Difference between revisions of "Mitochondria"

Latest revision as of 21:26, 30 November 2008

In cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed organelle found in most eukaryotic cells.^[1] These organelles range from 1–10 micrometers (μm) in size. Mitochondria are sometimes described as "cellular power plants" because they generate most of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy. In addition to supplying cellular energy, mitochondria are involved in a range of other processes, such as signaling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth.^[2] Mitochondria have been implicated in several human diseases, including mental disorders^[3] and cardiac dysfunction,^[4] and may play a role in the aging process. The word mitochondrion comes from the Greek μίτος or mitos, thread + χονδρίον or khondrion, granule. Their ancestry is not fully understood, but, according to the endosymbiotic theory, mitochondria are descended from ancient bacteria, which were engulfed by the ancestors of eukaryotic cells more than a billion years ago.

Several characteristics make mitochondria unique. The number of mitochondria in a cell varies widely by organism and tissue type. Many cells have only a single mitochondrion, whereas others can contain several thousand mitochondria.^[5]^[6] The organelle is composed of compartments that carry out specialized functions. These compartments or regions include the outer membrane, the intermembrane space, the inner membrane, and the cristae and matrix. Mitochondrial proteins vary depending on the tissues and species. In human, 615 distinct types of proteins were identified from cardiac mitochondria;^[7] whereas in murine, 940 proteins encoded by distinct genes were reported.^[8] The mitochondrial proteome is thought to be dynamically regulated.^[9] Although most of a cell's DNA is contained in the cell nucleus, the mitochondrion has its own independent genome. Further, its DNA shows substantial similarity to bacterial genomes.^[10]

Structure

File:Diagram of an animal mitochondrion svg.png

Simplified structure of mitochondrion

A mitochondrion contains outer and inner membranes composed of phospholipid bilayers and proteins.^[5] The two membranes, however, have different properties. Because of this double-membraned organization, there are five distinct compartments within the mitochondrion. There is the outer mitochondrial membrane, the intermembrane space (the space between the outer and inner membranes), the inner mitochondrial membrane, the cristae space (formed by infoldings of the inner membrane), and the matrix (space within the inner membrane).

Outer membrane

The outer mitochondrial membrane, which encloses the entire organelle, has a protein-to-phospholipid ratio similar to that of the eukaryotic plasma membrane (about 1:1 by weight). It contains large numbers of integral proteins called porins. These porins form channels that allow molecules 5000 Daltons or less in molecular weight to freely diffuse from one side of the membrane to the other.^[5] Larger proteins can also enter the mitochondrion if a signaling sequence at their N-terminus binds to a large multisubunit protein called translocase of the outer membrane, which then actively moves them across the membrane.^[11] Disruption of the outer membrane permits proteins in the intermembrane space to leak into the cytosol, leading to certain cell death.^[12]

Intermembrane space

The intermembrane space is basically the space between the outer membrane and the inner membrane. Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules such as ions and sugars in the intermembrane space is the same as the cytosol.^[5] However, as large proteins must have a specific signaling sequence to be transported across the outer membrane, the protein composition of this space is different than the protein composition of the cytosol. One protein that is localized to the intermembrane space in this way is cytochrome c.^[12]

Inner membrane

The inner mitochondrial membrane contains proteins with four types of functions:^[5]

Those that perform the redox reactions of oxidative phosphorylation
ATP synthase, which generates ATP in the matrix
Specific transport proteins that regulate metabolite passage into and out of the matrix
Protein import machinery.

It contains more than 100 different polypeptides, and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about 1 protein for 15 phospholipids). The inner membrane is home to around 1/5 of the total protein in a mitochondrion.^[5] In addition, the inner membrane is rich in an unusual phospholipid, cardiolipin. This phospholipid was originally discovered in beef hearts in 1942, and is usually characteristic of mitochondrial and bacterial plasma membranes.^[13] Cardiolipin contains four fatty acids rather than two and may help to make the inner membrane impermeable.^[5] Unlike the outer membrane, the inner membrane does not contain porins and is highly impermeable to all molecules. Almost all ions and molecules require special membrane transporters to enter or exit the matrix. Proteins are ferried into the matrix via the translocase of the inner membrane (TIM) complex or via Oxa1.^[11] In addition, there is a membrane potential across the inner membrane formed by the action of the enzymes of the electron transport chain.

Cristae

Cross-sectional image of cristae in rat liver mitochondrion to demonstrate the likely 3D structure and relationship to the inner membrane.

The inner mitochondrial membrane is compartmentalized into numerous cristae, which expand the surface area of the inner mitochondrial membrane, enhancing its ability to produce ATP. These are not simple random folds but rather invaginations of the inner membrane, which can affect overall chemiosmotic function.^[14] In typical liver mitochondria, for example, the surface area, including cristae, is about five times that of the outer membrane. Mitochondria of cells that have greater demand for ATP, such as muscle cells, contain more cristae than typical liver mitochondria.^[5]

Matrix

The matrix is the space enclosed by the inner membrane. It contains about 2/3 of the total protein in a mitochondrion.^[5] The matrix is important in the production of ATP with the aid of the ATP synthase contained in the inner membrane. The matrix contains a highly-concentrated mixture of hundreds of enzymes, special mitochondrial ribosomes, tRNA, and several copies of the mitochondrial DNA genome. Of the enzymes, the major functions include oxidation of pyruvate and fatty acids, and the citric acid cycle.^[5]

Mitochondria have their own genetic material, and the machinery to manufacture their own RNAs and proteins (see: protein biosynthesis). A published human mitochondrial DNA sequence revealed 16,569 base pairs encoding 37 total genes, 24 tRNA and rRNA genes and 13 peptide genes.^[15] The 13 mitochondrial peptides in humans are integrated into the inner mitochondrial membrane, along with proteins encoded by genes that reside in the host cell's nucleus.

Organization and distribution

Mitochondria are found in nearly all eukaryotes. They vary in number and location according to cell type. Substantial numbers of mitochondria are in the liver, with about 1000–2000 mitochondria per cell making up 1/5th of the cell volume.^[5] The mitochondria can be found nestled between myofibrils of muscle or wrapped around the sperm flagellum.^[5] Often they form a complex 3D branching network inside the cell with the cytoskeleton. The association with the cytoskeleton determines mitochondrial shape, which can affect the function as well.^[16] Recent evidence suggests vimentin, one of the components of the cytoskeleton, is critical to the association with the cytoskeleton.^[17]

Function

The most prominent roles of the mitochondrion are its production of ATP and regulation of cellular metabolism.^[6] The central set of reactions involved in ATP production are collectively known as the citric acid cycle, or the Krebs Cycle. However, the mitochondrion has many other functions in addition to the production of ATP.

Energy conversion

A dominant role for the mitochondria is the production of ATP, as reflected by the large number of proteins in the inner membrane for this task. This is done by oxidizing the major products of glucose, pyruvate, and NADH, which are produced in the cytosol.^[6] This process of cellular respiration, also known as aerobic respiration, is dependent on the presence of oxygen. When oxygen is limited, the glycolytic products will be metabolized by anaerobic respiration, a process that is independent of the mitochondria.^[6] The production of ATP from glucose has an approximately 13-fold higher yield during aerobic respiration compared to anaerobic respiration.^[18]

Pyruvate: the citric acid cycle

Each pyruvate molecule produced by glycolysis is actively transported across the inner mitochondrial membrane, and into the matrix where it is oxidized and combined with coenzyme A to form CO₂, acetyl-CoA, and NADH.^[6]

The acetyl-CoA is the primary substrate to enter the citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or Krebs cycle. The enzymes of the citric acid cycle are located in the mitochondrial matrix, with the exception of succinate dehydrogenase, which is bound to the inner mitochondrial membrane as part of Complex II.^[19] The citric acid cycle oxidizes the acetyl-CoA to carbon dioxide, and, in the process, produces reduced cofactors (three molecules of NADH and one molecule of FADH₂) that are a source of electrons for the electron transport chain, and a molecule of GTP (that is readily converted to an ATP).^[6]

NADH and FADH₂: the electron transport chain

미토콘드리아

File:Biological cell svg.png

Schematic of typical animal cell, showing subcellular components. Organelles:

(1) nucleolus
(2) nucleus
(3) ribosomes (little dots)
(4) vesicle
(5) rough endoplasmic reticulum (ER)
(6) Golgi apparatus
(7) Cytoskeleton
(8) smooth ER
(9) mitochondria
(10) vacuole
(11) cytoplasm
(12) lysosome

(13) centrioles within centrosome

The redox energy from NADH and FADH₂ is transferred to oxygen (O₂) in several steps via the electron transport chain. These energy-rich molecules are produced within the matrix via the citric acid cycle but are also produced in the cytoplasm by glycolysis. Reducing equivalents from the cytoplasm can be imported via the malate-aspartate shuttle system of antiporter proteins or feed into the electron transport chain using a glycerol phosphate shuttle.^[6] Protein complexes in the inner membrane (NADH dehydrogenase, cytochrome c reductase, and cytochrome c oxidase) perform the transfer and the incremental release of energy is used to pump protons (H⁺) into the intermembrane space. This process is efficient, but a small percentage of electrons may prematurely reduce oxygen, forming reactive oxygen species such as superoxide.^[6] This can cause oxidative stress in the mitochondria and may contribute to the decline in mitochondrial function associated with the aging process.^[20]

As the proton concentration increases in the intermembrane space, a strong electrochemical gradient is established across the inner membrane. The protons can return to the matrix through the ATP synthase complex, and their potential energy is used to synthesize ATP from ADP and inorganic phosphate (P_i).^[6] This process is called chemiosmosis, and was first described by Peter Mitchell^[21]^[22] who was awarded the 1978 Nobel Prize in Chemistry for his work. Later, part of the 1997 Nobel Prize in Chemistry was awarded to Paul D. Boyer and John E. Walker for their clarification of the working mechanism of ATP synthase.^[23]

Heat production

Under certain conditions, protons can re-enter the mitochondrial matrix without contributing to ATP synthesis. This process is known as proton leak or mitochondrial uncoupling and is due to the facilitated diffusion of protons into the matrix. The process results in the unharnessed potential energy of the proton electrochemical gradient being released as heat.^[6] The process is mediated by a proton channel called thermogenin, or UCP1.^[24] Thermogenin is a 33kDa protein first discovered in 1973.^[25] Thermogenin is primarily found in brown adipose tissue, or brown fat, and is responsible for non-shivering thermogenesis. Brown adipose tissue is found in mammals, and is at its highest levels in early life and in hibernating animals. In humans, brown adipose tissue is present at birth and decreases with age.^[24]

Storage of calcium ions

The concentrations of free calcium in the cell can regulate an array of reactions and is important for signal transduction in the cell. Mitochondria can transiently store calcium, a contributing process for the cell's homeostasis of calcium.^[26] In fact, their ability to rapidly take in calcium for later release makes them very good "cytosolic buffers" for calcium.^[27] The endoplasmic reticulum (ER) is the most significant storage site of calcium, and there is a significant interplay between the mitochondrion and ER with regard to calcium.^[28] The calcium is taken up into the matrix by a calcium uniporter on the inner mitochondrial membrane.^[29] It is primarily driven by the mitochondrial membrane potential.^[26] Release of this calcium back into the cell's interior can occur via a sodium-calcium exchange protein or via "calcium-induced-calcium-release" pathways.^[29] This can initiate calcium spikes or calcium waves with large changes in the membrane potential. These can activate a series of second messenger system proteins that can coordinate processes such as neurotransmitter release in nerve cells and release of hormones in endocrine cells.

Additional functions

Mitochondria play a central role in many other metabolic tasks, such as:

Regulation of the membrane potential^[6]
Apoptosis-programmed cell death^[30]
Glutamate-mediated excitotoxic neuronal injury^[31]
Cellular proliferation regulation^[32]
Regulation of cellular metabolism^[32]
Certain heme synthesis reactions^[33] (see also: porphyrin)
Steroid synthesis.^[27]

Some mitochondrial functions are performed only in specific types of cells. For example, mitochondria in liver cells contain enzymes that allow them to detoxify ammonia, a waste product of protein metabolism. A mutation in the genes regulating any of these functions can result in mitochondrial diseases.

Origin

Mitochondria have many features in common with prokaryotes. As a result, they are believed to be originally derived from endosymbiotic prokaryotes.

A mitochondrion contains DNA, which is organized as several copies of a single, circular chromosome. This mitochondrial chromosome contains genes for ribosomes, and the twenty-one tRNA's necessary for the translation of messenger RNAs into protein. The circular structure is also found in prokaryotes, and the similarity is extended by the fact that mitochondrial DNA is organized with a variant genetic code similar to that of Proteobacteria.^[34] This suggests that their ancestor, the so-called proto-mitochondrion, was a member of the Proteobacteria.^[34] In particular, the proto-mitochondrion was probably related to the rickettsia.^[35] However, the exact relationship of the ancestor of mitochondria to the alpha-proteobacteria and whether the mitochondria was formed at the same time or after the nucleus, remains controversial.^[36]

The ribosomes coded for by the mitochondrial DNA are similar to those from bacteria in size and structure.^[37] They closely resemble the bacterial 70S ribosome and not the 80S cytoplasmic ribosomes which are coded for by nuclear DNA.

The endosymbiotic relationship of mitochondria with their host cells was popularized by Lynn Margulis.^[38] The endosymbiotic hypothesis suggests that mitochondria descended from bacteria that somehow survived endocytosis by another cell, and became incorporated into the cytoplasm. The ability of these bacteria to conduct respiration in host cells that had relied on glycolysis and fermentation would have provided a considerable evolutionary advantage. In a similar manner, host cells with symbiotic bacteria capable of photosynthesis would also have had an advantage. The incorporation of symbiotes would have increased the number of environments in which the cells could survive. This symbiotic relationship probably developed 1.7^[39]-2^[40] billion years ago.

A few groups of unicellular eukaryotes lack mitochondria: the microsporidians, metamonads, and archamoebae.^[41] These groups appear as the most primitive eukaryotes on phylogenetic trees constructed using rRNA information, suggesting that they appeared before the origin of mitochondria. However, this is now known to be an artifact of long-branch attraction – they are derived groups and retain genes or organelles derived from mitochondria (e.g., mitosomes and hydrogenosomes).^[1]

Genome

The human mitochondrial genome is a circular DNA molecule of about 16 kilobases.^[42] It encodes 37 genes: 13 for subunits of respiratory complexes I, III, IV and V, 22 for mitochondrial tRNA, and 2 for rRNA.^[42] One mitochondrion can contain two to ten copies of its DNA.^[43]

As in prokaryotes, there is a very high proportion of coding DNA and an absence of repeats. Mitochondrial genes are transcribed as multigenic transcripts, which are cleaved and polyadenylated to yield mature mRNAs. Not all proteins necessary for mitochondrial function are encoded by the mitochondrial genome; most are coded by genes in the cell nucleus and the corresponding proteins imported into the mitochondrion.^[44] The exact number of genes encoded by the nucleus and the mitochondrial genome differs between species. In general, mitochondrial genomes are circular, although exceptions have been reported.^[45] Also, in general, mitochondrial DNA lacks introns, as is the case in the human mitochondrial genome;^[44] however, introns have been observed in some eukaryotic mitochondrial DNA,^[46] such as that of yeast^[47] and protists,^[48] including Dictyostelium discoideum.^[49]

While slight variations on the standard code had been predicted earlier,^[50] none was discovered until 1979, when researchers studying human mitochondrial genes determined that they used an alternative code.^[51] Many slight variants have been discovered since,^[52] including various alternative mitochondrial codes.^[53] Further, the AUA, AUC, and AUU codons are all allowable start codons.

Exceptions to the universal genetic code (UGC) in mitochondria^[5]
Organism	Codon	Standard	Novel
Mammalian	AGA, AGG	Arginine	Stop codon
	AUA	Isoleucine	Methionine
	UGA	Stop codon	Tryptophan
Invertebrates	AGA, AGG	Arginine	Serine
	AUA	Isoleucine	Methionine
	UGA	Stop codon	Tryptophan
Yeast	AUA	Isoleucine	Methionine
	UGA	Stop codon	Tryptophan
	CUA	Leucine	Threonine

Some of these differences should be regarded as pseudo-changes in the genetic code due to the phenomenon of RNA editing, which is common in mitochondria. In higher plants, it was thought that CGG encoded for tryptophan and not arginine; however, the codon in the processed RNA was discovered to be the UGG codon, consistent with the universal genetic code for tryptophan.^[54] Of note, the arthropod mitochondrial genetic code has undergone parallel evolution within a phylum, with some organisms uniquely translating AGG to lysine.^[55]

Mitochondrial genomes have far fewer genes than the bacteria from which they are thought to be descended. Although some have been lost altogether, many have been transferred to the nucleus, such as the respiratory complex II protein subunits.^[42] This is thought to be relatively common over evolutionary time. A few organisms, such as the Cryptosporidium, actually have mitochondria that lack any DNA, presumably because all their genes have been lost or transferred.^[56] In Cryptosporidium, the mitochondria have an altered ATP generation system that renders the parasite resistant to many classical mitochondrial inhibitors such as cyanide, azide, and atovaquone.^[56]

Replication and inheritance

Mitochondria divide by binary fission similar to bacterial cell division; unlike bacteria, however, mitochondria can also fuse with other mitochondria.^[42]^[57]. The regulation of this division differs between eukaryotes. In many single-celled eukaryotes, their growth and division is linked to the cell cycle. For example, a single mitochondrion may divide synchronously with the nucleus. This division and segregation process must be tightly controlled so that each daughter cell receives at least one mitochondrion. In other eukaryotes (in humans for example), mitochondria may replicate their DNA and divide mainly in response to the energy needs of the cell, rather than in phase with the cell cycle. When the energy needs of a cell are high, mitochondria grow and divide. When the energy use is low, mitochondria are destroyed or become inactive. In such examples, and in contrast to the situation in many single celled eukaryotes, mitochondria are apparently randomly distributed to the daughter cells during the division of the cytoplasm.

An individual's mitochondrial genes are not inherited by the same mechanism as nuclear genes. At fertilization of an egg cell by a sperm, the egg nucleus and sperm nucleus each contribute equally to the genetic makeup of the zygote nucleus. In contrast, the mitochondria, and therefore the mitochondrial DNA, usually comes from the egg only. The sperm's mitochondria enter the egg but does not contribute genetic information to the embryo.^[58] Instead, paternal mitochondria are marked with ubiquitin to select them for later destruction inside the embryo.^[59] The egg cell contains relatively few mitochondria, but it is these mitochondria that survive and divide to populate the cells of the adult organism. Mitochondria are, therefore, in most cases inherited down the female line, known as maternal inheritance. This mode is seen in most organisms including all animals. However, mitochondria in some species can sometimes be inherited paternally. This is the norm among certain coniferous plants, although not in pine trees and yew trees.^[60] It has also been suggested that it occurs at a very low level in humans.^[61]

Uniparental inheritance leads to little opportunity for genetic recombination between different lineages of mitochondria, although a single mitochondrion can contain 2–10 copies of its DNA.^[43] For this reason, mitochondrial DNA usually is thought to reproduce by binary fission. What recombination does take place maintains genetic integrity rather than maintaining diversity. However, there are studies showing evidence of recombination in mitochondrial DNA. It is clear that the enzymes necessary for recombination are present in mammalian cells.^[62] Further, evidence suggests that animal mitochondria can undergo recombination.^[63] The data are a bit more controversial in humans, although indirect evidence of recombination exists.^[64]^[65] If recombination does not occur, the whole mitochondrial DNA sequence represents a single haplotype, which makes it useful for studying the evolutionary history of populations.

Population genetic studies

The near-absence of genetic recombination in mitochondrial DNA makes it a useful source of information for scientists involved in population genetics and evolutionary biology.^[66] Because all the mitochondrial DNA is inherited as a single unit, or haplotype, the relationships between mitochondrial DNA from different individuals can be represented as a gene tree. Patterns in these gene trees can be used to infer the evolutionary history of populations. The classic example of this is in human evolutionary genetics, where the molecular clock can be used to provide a recent date for mitochondrial Eve.^[67]^[68] This is often interpreted as strong support for a recent modern human expansion out of Africa.^[69] Another human example is the sequencing of mitochondrial DNA from Neanderthal bones. The relatively-large evolutionary distance between the mitochondrial DNA sequences of Neanderthals and living humans has been interpreted as evidence for lack of interbreeding between Neanderthals and anatomically-modern humans.^[70]

However, mitochondrial DNA reflects the history of only females in a population and so may not represent the history of the population as a whole. This can be partially overcome by the use of paternal genetic sequences, such as the non-recombining region of the Y-chromosome.^[69] In a broader sense, only studies that also include nuclear DNA can provide a comprehensive evolutionary history of a population.^[71]

Dysfunction and disease

Mitochondrial diseases

With their central place in cell metabolism, damage - and subsequent dysfunction - in mitochondria is an important factor in a wide range of human diseases. Mitochondrial disorders often present as neurological disorders, but can manifest as myopathy, diabetes, multiple endocrinopathy, or a variety of other systemic manifestations.^[72] Diseases caused by mutation in the mtDNA include Kearns-Sayre syndrome, MELAS syndrome and Leber's hereditary optic neuropathy.^[73] In the vast majority of cases, these diseases are transmitted by a female to her children, as the zygote derives its mitochondria and hence its mtDNA from the ovum. Diseases such as Kearns-Sayre syndrome, Pearson's syndrome, and progressive external ophthalmoplegia are thought to be due to large-scale mtDNA rearrangements, whereas other diseases such as MELAS syndrome, Leber's hereditary optic neuropathy, myoclonic epilepsy with ragged red fibers (MERRF), and others are due to point mutations in mtDNA.^[72]

In other diseases, defects in nuclear genes lead to dysfunction of mitochondrial proteins. This is the case in Friedreich's ataxia, hereditary spastic paraplegia, and Wilson's disease.^[74] These diseases are inherited in a dominance relationship, as applies to most other genetic diseases. A variety of disorders can be caused by nuclear mutations of oxidative phosphorylation enzymes, such as coenzyme Q10 deficiency and Barth syndrome.^[72] Environmental influences may also interact with hereditary predispositions and cause mitochondrial disease. For example, there may be a link between pesticide exposure and the later onset of Parkinson's disease.^[75]^[76]

Other diseases not directly linked to mitochondrial enzymes may feature dysfunction of mitochondria. These include schizophrenia, bipolar disorder, dementia, Alzheimer's disease, Parkinson's disease, epilepsy, stroke, cardiovascular disease, retinitis pigmentosa, and diabetes mellitus.^[77]^[78] The common thread linking these seemingly-unrelated conditions is cellular damage causing oxidative stress and the accumulation of reactive oxygen species. These oxidants then damage the mitochondrial DNA, resulting in mitochondrial dysfunction and cell death.^[78]

Possible relationships to aging

Given the role of mitochondria as the cell's powerhouse, there may be some leakage of the high-energy electrons in the respiratory chain to form reactive oxygen species. This can result in significant oxidative stress in the mitochondria with high mutation rates of mitochondrial DNA.^[79] A vicious cycle is thought to occur, as oxidative stress leads to mitochondrial DNA mutations, which can lead to enzymatic abnormalities and further oxidative stress. A number of changes occur to mitochondria during the aging process.^[80] Tissues from elderly patients show a decrease in enzymatic activity of the proteins of the respiratory chain.^[81] Large deletions in the mitochondrial genome can lead to high levels of oxidative stress and neuronal death in Parkinson's disease.^[82] Hypothesized links between aging and oxidative stress are not new and were proposed over 50 years ago;^[83] however, there is much debate over whether mitochondrial changes are causes of aging or merely characteristics of aging. One notable study in mice demonstrated no increase in reactive oxygen species despite increasing mitochondrial DNA mutations, suggesting that the aging process is not due to oxidative stress.^[84] As a result, the exact relationships between mitochondria, oxidative stress, and aging have not yet been settled.

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External links

Mitochondria Atlas at University of Mainz
Mitochondria Research Portal at mitochondrial.net
Mitochondria: Architecture dictates function at cytochemistry.net
Mitochondria links at University of Alabama
MIP Mitochondrial Physiology Society
Mitochondrion Reconstructed by Electron Tomography at San Diego State University
Video Clip of Rat-liver Mitochondrion from Cryo-electron Tomography at wadsworth.org
3D structures of proteins from inner mitochondrial membrane at University of Michigan
3D structures of proteins associated with outer mitochondrial membrane at University of Michigan

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[McBride-31] McBride HM, Neuspiel M, Wasiak S (2006 July). "Mitochondria: more than just a powerhouse". Curr Biol. 16 (14): R551–60. doi:10.1016/j.cub.2006.06.054. PMID 16860735.

[32] Oh-hama T (1997 August). "Evolutionary consideration on 5-aminolevulinate synthase in nature". Orig Life Evol Biosph. 27 (4): 405–12. doi:10.1023/A:1006583601341. PMID 9249985.

[Shoulders1-33] Futuyma DJ (2005). "On Darwin's Shoulders". Natural History 114 (9): 64–68.

[34] Emelyanov VV (2003). "Mitochondrial connection to the origin of the eukaryotic cell". Eu J Biochem. 270 (8): 1599–1618. doi:10.1046/j.1432-1033.2003.03499.x.

[35] Gray MW, Burger G, Lang BF (March 1999). "Mitochondrial evolution". Science (journal) 283 (5407): 1476–81. PMID 10066161.

[36] O'Brien TW (2003 September). "Properties of human mitochondrial ribosomes". IUBMB Life. 55 (9): 505–13. doi:10.1080/15216540310001626610.

[37] Lynn Sagan (1967). "On the origin of mitosing cells". J Theor Bio. 14 (3): 255–274. doi:10.1016/0022-5193(67)90079-3. PMID 11541392.

[38] Emelyanov VV (2001). "Rickettsiaceae, rickettsia-like endosymbionts, and the origin of mitochondria". Biosci. Rep. 21: 1–17. doi:10.1023/A:1010409415723. PMID 11508688.

[39] Feng D-F, Cho G, Doolittle RF (1997). "Determining divergence times with a protein clock: update and reevaluation". Proc. Natl Acad. Sci. 94: 13028–13033. doi:10.1073/pnas.94.24.13028. PMID 9371794.

[Cavlier-Smith-40] Cavalier-Smith T (1991). "Archamoebae: the ancestral eukaryotes?". Biosystems. 25: 1241. doi:10.1016/0303-2647(91)90010-I. PMID 1854912.

[ChanDC-41] Chan DC (2006-06-30). "Mitochondria: Dynamic Organelles in Disease, Aging, and Development". Cell 125 (7): 1241–1252. doi:10.1016/j.cell.2006.06.010. PMID 16814712.

[Wiesner-42] Wiesner RJ, Ruegg JC, Morano I (1992). "Counting target molecules by exponential polymerase chain reaction, copy number of mitochondrial DNA in rat tissues". Biochim Biophys Acta 183: 553–559. PMID 1550563.

[Anderson-43] Anderson S, Bankier AT, Barrell BG, de-Bruijn MHL, Coulson AR, et al. (1981). "Sequence and organization of the human mitochondrial genome". Nature 290: 427–465. doi:10.1038/290457a0.

[Fukuhara-44] Fukuhara H, Sor F, Drissi R, Dinouël N, Miyakawa I, Rousset, and Viola AM (1993). "Linear mitochondrial DNAs of yeasts: frequency of occurrence and general features". Mol Cell Biol. 13 (4): 2309–2314. PMID 8455612.

[45] Bernardi G (1978). "Intervening sequences in the mitochondrial genome". Nature. 276 (5688): 558–559. doi:10.1038/276558a0. PMID 214710.

[46] Hebbar SK, Belcher SM, Perlman PS (1992 April). "A maturase-encoding group IIA intron of yeast mitochondria self-splices in vitro". Nucleic Acids Res. 20 (7): 1747–54. doi:10.1093/nar/20.7.1747. PMID 1579468.

[47] Gray MW, Lang BF, Cedergren R, Golding GB, Lemieux C, Sankoff D, et al (1998). "Genome structure and gene content in protist mitochondrial DNAs". Nucl Acids Res. 26 (4): 865–878. doi:10.1093/nar/26.4.865. PMID 9461442.

[48] Gray MW, Lang BF, Burger G (2004). "Mitochondria of protists". Ann Rev of Genetics. 38: 477–524. doi:10.1146/annurev.genet.37.110801.142526. PMID 15568984.

[49] Crick, F. H. C. and Orgel, L. E. (1973) "Directed panspermia." Icarus 19:341-346. p. 344: "It is a little surprising that organisms with somewhat different codes do not coexist." (Further discussion at [1])

[50] Barrell BG, Bankier AT, Drouin J (1979). "A different genetic code in human mitochondria". Nature. 282: 189–194. doi:10.1038/282189a0.

[51] NCBI: "The Genetic Codes", Compiled by Andrzej (Anjay) Elzanowski and Jim Ostell

[52] Jukes TH, Osawa S (1990-12-01). "The genetic code in mitochondria and chloroplasts". Experientia. 46 (11–12): 1117–26. doi:10.1007/BF01936921. PMID 2253709.

[53] Hiesel R, Wissinger B, Schuster W, Brennicke A (2006). "RNA editing in plant mitochondria". Science. 246 (4937): 1632–4. doi:10.1126/science.2480644. PMID 2480644.

[54] Abascal F, Posada D, Knight RD, Zardoya R (2006). "Parallel Evolution of the Genetic Code in Arthropod Mitochondrial Genomes". PLoS Biology. 4 (5): 0711–0718. doi:10.1371/journal.pbio.0040127. PMID 16620150.

[Henriquez-55] Henriquez FL, Richards TA, Roberts F, McLeod R, Roberts CW (2005 February). "The unusual mitochondrial compartment of Cryptosporidium parvum". Trends Parasitol. 21 (2): 68–74. doi:10.1016/j.pt.2004.11.010. PMID 15664529.

[56] Hermann GJ, Thatcher JW, Mills JP, Hales KG, Fuller MT, Nunnari J, Shaw JM (1998 October). "Mitochondrial Fusion in Yeast Requires the Transmembrane GTPase Fzo1p". J. Cell. Bio. 143 (2): 359–373. doi:10.1083/jcb.143.2.359. PMID 9786948.

[57] Kimball, J.W. (2006) "Sexual Reproduction in Humans: Copulation and Fertilization," Kimball's Biology Pages (based on Biology, 6th ed., 1996)]

[58] Sutovsky, P., et. al (1999). "Ubiquitin tag for sperm mitochondria". Nature 402: 371–372. doi:10.1038/46466. Discussed in Science News.

[59] Mogensen HL (1996). "The Hows and Whys of Cytoplasmic Inheritance in Seed Plants". American Journal of Botany 83: 247. doi:10.2307/2446172.

[60] Johns, D. R. (2003). "Paternal transmission of mitochondrial DNA is (fortunately) rare". Annals of Neurology 54: 422–4. doi:10.1002/ana.10771. PMID 14520651.

[61] Thyagarajan B, Padua RA, Campbell C (1996). "Mammalian mitochondria possess homologous DNA recombination activity". J. Biol. Chem. 271 (44): 27536–27543. doi:10.1074/jbc.271.44.27536. PMID 8910339.

[62] Lunt DB, Hyman BC (15 May 1997). "Animal mitochondrial DNA recombination". Nature 387: 247. doi:10.1038/387247a0. PMID 9153388.

[63] Eyre-Walker A, Smith NH, Maynard Smith J (1999-03-07). "How clonal are human mitochondria?". Proc. Royal Soc. Biol. Sci. (Series B) 266 (1418): 477–483. doi:10.1098/rspb.1999.0662. PMID 10189711.

[64] Awadalla P, Eyre-Walker A, Maynard Smith J (24 December 1999). "Linkage Disequilibrium and Recombination in Hominid Mitochondrial DNA". Science. 286 (5449): 2524–2525. doi:10.1126/science.286.5449.2524. PMID 10617471.

[65] Castro JA, Picornell A, Ramon M (1998). "Mitochondrial DNA: a tool for populational genetics studies". Int Microbiol. 1 (4): 327–32. PMID 10943382.

[66] Cann RL, Stoneking M, Wilson AC (1987 January). "Mitochondrial DNA and human evolution". Nature. 325: 31–36. doi:10.1038/325031a0.

[67] Torroni A, Achilli A, Macaulay V, Richards M, Bandelt HJ (2006). "Harvesting the fruit of the human mtDNA tree". Trends Genet. 22 (6): 339–45. doi:10.1016/j.tig.2006.04.001. PMID 16678300.

[Garrigan06-68] Garrigan D, Hammer MF (2006). "Reconstructing human origins in the genomic era". Nat. Rev. Genet. 7 (9): 669–80. doi:10.1038/nrg1941. PMID 16921345.

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Difference between revisions of "Mitochondria"

Latest revision as of 21:26, 30 November 2008

Contents

Structure

Outer membrane

Intermembrane space

Inner membrane

Cristae

Matrix

Organization and distribution

Function

Energy conversion

Pyruvate: the citric acid cycle

NADH and FADH₂: the electron transport chain

미토콘드리아

Heat production

Storage of calcium ions

Additional functions

Origin

Genome

Replication and inheritance

Population genetic studies

Dysfunction and disease

Mitochondrial diseases

Possible relationships to aging

References

See also

External links

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@@ Line 1: / Line 1: @@
+<p>In cell biology, a <strong>mitochondrion</strong> (plural <strong>mitochondria</strong>) is a membrane-enclosed organelle found in most eukaryotic cells.<sup class="reference" id="cite_ref-mitosomes_0-0"><span>[</span>1<span>]</span></sup> These organelles range from 1&ndash;10&nbsp;micrometers (&mu;m) in size. Mitochondria are sometimes described as &quot;cellular power plants&quot; because they generate most of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy. In addition to supplying cellular energy, mitochondria are involved in a range of other processes, such as signaling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth.<sup class="reference" id="cite_ref-1"><span>[</span>2<span>]</span></sup> Mitochondria have been implicated in several human diseases, including mental disorders<sup class="reference" id="cite_ref-2"><span>[</span>3<span>]</span></sup> and cardiac dysfunction,<sup class="reference" id="cite_ref-3"><span>[</span>4<span>]</span></sup> and may play a role in the aging process. The word mitochondrion comes from the Greek <em>&mu;ί&tau;&omicron;&sigmaf;</em> or <em>mitos</em>, thread + <em>&chi;&omicron;&nu;&delta;&rho;ί&omicron;&nu;</em> or <em>khondrion</em>, granule. Their ancestry is not fully understood, but, according to the endosymbiotic theory, mitochondria are descended from ancient bacteria, which were engulfed by the ancestors of eukaryotic cells more than a billion years ago.</p>
+<p>Several characteristics make mitochondria unique. The number of mitochondria in a cell varies widely by organism and tissue type. Many cells have only a single mitochondrion, whereas others can contain several thousand mitochondria.<sup class="reference" id="cite_ref-Alberts_4-0"><span>[</span>5<span>]</span></sup><sup class="reference" id="cite_ref-Voet_5-0"><span>[</span>6<span>]</span></sup> The organelle is composed of compartments that carry out specialized functions. These compartments or regions include the outer membrane, the intermembrane space, the inner membrane, and the cristae and matrix. Mitochondrial proteins vary depending on the tissues and species. In human, 615 distinct types of proteins were identified from cardiac mitochondria;<sup class="reference" id="cite_ref-6"><span>[</span>7<span>]</span></sup> whereas in murine, 940 proteins encoded by distinct genes were reported.<sup class="reference" id="cite_ref-7"><span>[</span>8<span>]</span></sup> The mitochondrial proteome is thought to be dynamically regulated.<sup class="reference" id="cite_ref-8"><span>[</span>9<span>]</span></sup> Although most of a cell's DNA is contained in the cell nucleus, the mitochondrion has its own independent genome. Further, its DNA shows substantial similarity to bacterial genomes.<sup class="reference" id="cite_ref-9"><span>[</span>10<span>]</span></sup></p>
+<p>&nbsp;</p>
+<p>&nbsp;</p>
+<h2><span class="mw-headline">Structure</span></h2>
+<div class="thumb tright">
+<div class="thumbinner" style="WIDTH: 417px">
+<div><map id="ImageMap_1" name="ImageMap_1">
+<area title="ATP synthase" alt="ATP synthase" href="/wiki/ATP_synthase" coords="195,35,329,61" shape="RECT" />
+<area title="Intermembrane space of mitochondria" alt="Intermembrane space of mitochondria" href="/wiki/Intermembrane_space_of_mitochondria" coords="67,74,196,95" shape="RECT" />
+<area title="Mitochondrial matrix" alt="Mitochondrial matrix" href="/wiki/Mitochondrial_matrix" coords="154,96,202,115" shape="RECT" />
+<area title="Crista" alt="Crista" href="/wiki/Crista" coords="76,135,125,155" shape="RECT" />
+<area title="Ribosome" alt="Ribosome" href="/wiki/Ribosome" coords="17,143,81,165" shape="RECT" />
+<area title="Granules" alt="Granules" href="/wiki/Granules" coords="10,171,75,194" shape="RECT" />
+<area title="Mitochondrial DNA" alt="Mitochondrial DNA" href="/wiki/Mitochondrial_DNA" coords="250,264,307,300" shape="RECT" />
+<area title="Inner mitochondrial membrane" alt="Inner mitochondrial membrane" href="/wiki/Inner_mitochondrial_membrane" coords="324,237,442,262" shape="RECT" />
+<area title="Outer mitochondrial membrane" alt="Outer mitochondrial membrane" href="/wiki/Outer_mitochondrial_membrane" coords="317,261,439,287" shape="RECT" /></map></div>
+<div class="thumbcaption">
+<div class="magnify">[[Image:Diagram of an animal mitochondrion svg.png]]</div>
+Simplified structure of mitochondrion</div>
+</div>
+</div>
+<p>A mitochondrion contains outer and inner membranes composed of phospholipid bilayers and proteins.<sup class="reference" id="cite_ref-Alberts_4-1"><span>[</span>5<span>]</span></sup> The two membranes, however, have different properties. Because of this double-membraned organization, there are five distinct compartments within the mitochondrion. There is the outer mitochondrial membrane, the intermembrane space (the space between the outer and inner membranes), the inner mitochondrial membrane, the cristae space (formed by infoldings of the inner membrane), and the matrix (space within the inner membrane).</p>
+<p>&nbsp;</p>
+<h3><span class="mw-headline">Outer membrane</span></h3>
+<dl><dd>
+<div class="noprint relarticle mainarticle">&nbsp;</div>
+</dd></dl>
+<p>The outer mitochondrial membrane, which encloses the entire organelle, has a protein-to-phospholipid ratio similar to that of the eukaryotic plasma membrane (about 1:1 by weight). It contains large numbers of integral proteins called <em>porins</em>. These porins form channels that allow molecules 5000&nbsp;Daltons or less in molecular weight to freely diffuse from one side of the membrane to the other.<sup class="reference" id="cite_ref-Alberts_4-2"><span>[</span>5<span>]</span></sup> Larger proteins can also enter the mitochondrion if a signaling sequence at their N-terminus binds to a large multisubunit protein called translocase of the outer membrane, which then actively moves them across the membrane.<sup class="reference" id="cite_ref-Neupert_10-0"><span>[</span>11<span>]</span></sup> Disruption of the outer membrane permits proteins in the intermembrane space to leak into the cytosol, leading to certain cell death.<sup class="reference" id="cite_ref-Chipuk_11-0"><span>[</span>12<span>]</span></sup></p>
+<p>&nbsp;</p>
+<h3><span class="mw-headline">Intermembrane space</span></h3>
+<p>The intermembrane space is basically the space between the outer membrane and the inner membrane. Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules such as ions and sugars in the intermembrane space is the same as the cytosol.<sup class="reference" id="cite_ref-Alberts_4-3"><span>[</span>5<span>]</span></sup> However, as large proteins must have a specific signaling sequence to be transported across the outer membrane, the protein composition of this space is different than the protein composition of the cytosol. One protein that is localized to the intermembrane space in this way is cytochrome c.<sup class="reference" id="cite_ref-Chipuk_11-1"><span>[</span>12<span>]</span></sup></p>
+<p>&nbsp;</p>
+<h3><span class="mw-headline">Inner membrane</span></h3>
+<dl><dd>
+<div class="noprint relarticle mainarticle">&nbsp;</div>
+</dd></dl>
+<p>The inner mitochondrial membrane contains proteins with four types of functions:<sup class="reference" id="cite_ref-Alberts_4-4"><span>[</span>5<span>]</span></sup></p>
+<ol>
+    <li>Those that perform the redox reactions of oxidative phosphorylation </li>
+    <li>ATP synthase, which generates ATP in the matrix </li>
+    <li>Specific transport proteins that regulate metabolite passage into and out of the matrix </li>
+    <li>Protein import machinery. </li>
+</ol>
+<p>It contains more than 100 different polypeptides, and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about 1&nbsp;protein for 15&nbsp;phospholipids). The inner membrane is home to around 1/5 of the total protein in a mitochondrion.<sup class="reference" id="cite_ref-Alberts_4-5"><span>[</span>5<span>]</span></sup> In addition, the inner membrane is rich in an unusual phospholipid, cardiolipin. This phospholipid was originally discovered in beef hearts in 1942, and is usually characteristic of mitochondrial and bacterial plasma membranes.<sup class="reference" id="cite_ref-McMillin_12-0"><span>[</span>13<span>]</span></sup> Cardiolipin contains four fatty acids rather than two and may help to make the inner membrane impermeable.<sup class="reference" id="cite_ref-Alberts_4-6"><span>[</span>5<span>]</span></sup> Unlike the outer membrane, the inner membrane does not contain porins and is highly impermeable to all molecules. Almost all ions and molecules require special membrane transporters to enter or exit the matrix. Proteins are ferried into the matrix via the translocase of the inner membrane (TIM) complex or via Oxa1.<sup class="reference" id="cite_ref-Neupert_10-1"><span>[</span>11<span>]</span></sup> In addition, there is a membrane potential across the inner membrane formed by the action of the enzymes of the electron transport chain.</p>
+<p>&nbsp;</p>
+<h4><span class="mw-headline">Cristae</span></h4>
+<dl><dd>
+<div class="noprint relarticle mainarticle">&nbsp;</div>
+</dd></dl>
+<div class="thumb tleft">
+<div class="thumbinner" style="WIDTH: 252px"><img class="thumbimage" height="165" alt="" width="250" border="0" src="http://upload.wikimedia.org/wikipedia/en/thumb/d/d8/MitochondrionCAM.jpg/250px-MitochondrionCAM.jpg" />
+<div class="thumbcaption">
+<div class="magnify"><img height="11" alt="" width="15" src="http://upload.wikimedia.org/skins/common/images/magnify-clip.png" /></div>
+Cross-sectional image of cristae in rat liver mitochondrion to demonstrate the likely 3D structure and relationship to the inner membrane.</div>
+</div>
+</div>
+<p>The inner mitochondrial membrane is compartmentalized into numerous cristae, which expand the surface area of the inner mitochondrial membrane, enhancing its ability to produce ATP. These are not simple random folds but rather invaginations of the inner membrane, which can affect overall chemiosmotic function.<sup class="reference" id="cite_ref-Mannella_13-0"><span>[</span>14<span>]</span></sup> In typical liver mitochondria, for example, the surface area, including cristae, is about five times that of the outer membrane. Mitochondria of cells that have greater demand for ATP, such as muscle cells, contain more cristae than typical liver mitochondria.<sup class="reference" id="cite_ref-Alberts_4-7"><span>[</span>5<span>]</span></sup></p>
+<p>&nbsp;</p>
+<h3><span class="mw-headline">Matrix</span></h3>
+<dl><dd>
+<div class="noprint relarticle mainarticle">&nbsp;</div>
+</dd></dl>
+<p>The matrix is the space enclosed by the inner membrane. It contains about 2/3 of the total protein in a mitochondrion.<sup class="reference" id="cite_ref-Alberts_4-8"><span>[</span>5<span>]</span></sup> The matrix is important in the production of ATP with the aid of the ATP synthase contained in the inner membrane. The matrix contains a highly-concentrated mixture of hundreds of enzymes, special mitochondrial ribosomes, tRNA, and several copies of the mitochondrial DNA genome. Of the enzymes, the major functions include oxidation of pyruvate and fatty acids, and the citric acid cycle.<sup class="reference" id="cite_ref-Alberts_4-9"><span>[</span>5<span>]</span></sup></p>
+<p>Mitochondria have their own genetic material, and the machinery to manufacture their own RNAs and proteins (<em>see: protein biosynthesis</em>). A published human mitochondrial DNA sequence revealed 16,569&nbsp;base pairs encoding 37 total genes, 24&nbsp;tRNA and rRNA genes and 13&nbsp;peptide genes.<sup class="reference" id="cite_ref-14"><span>[</span>15<span>]</span></sup> The 13 mitochondrial peptides in humans are integrated into the inner mitochondrial membrane, along with proteins encoded by genes that reside in the host cell's nucleus.</p>
+<p>&nbsp;</p>
+<h2><span class="mw-headline">Organization and distribution</span></h2>
+<p>Mitochondria are found in nearly all eukaryotes. They vary in number and location according to cell type. Substantial numbers of mitochondria are in the liver, with about 1000&ndash;2000 mitochondria per cell making up 1/5th of the cell volume.<sup class="reference" id="cite_ref-Alberts_4-10"><span>[</span>5<span>]</span></sup> The mitochondria can be found nestled between myofibrils of muscle or wrapped around the sperm flagellum.<sup class="reference" id="cite_ref-Alberts_4-11"><span>[</span>5<span>]</span></sup> Often they form a complex 3D branching network inside the cell with the cytoskeleton. The association with the cytoskeleton determines mitochondrial shape, which can affect the function as well.<sup class="reference" id="cite_ref-15"><span>[</span>16<span>]</span></sup> Recent evidence suggests vimentin, one of the components of the cytoskeleton, is critical to the association with the cytoskeleton.<sup class="reference" id="cite_ref-16"><span>[</span>17<span>]</span></sup></p>
+<p>&nbsp;</p>
+<h2><span class="mw-headline">Function</span></h2>
+<p>The most prominent roles of the mitochondrion are its production of ATP and regulation of cellular metabolism.<sup class="reference" id="cite_ref-Voet_5-1"><span>[</span>6<span>]</span></sup> The central set of reactions involved in ATP production are collectively known as the citric acid cycle, or the Krebs Cycle. However, the mitochondrion has many other functions in addition to the production of ATP.</p>
+<p>&nbsp;</p>
+<h3><span class="mw-headline">Energy conversion</span></h3>
+<p>A dominant role for the mitochondria is the production of ATP, as reflected by the large number of proteins in the inner membrane for this task. This is done by oxidizing the major products of glucose, pyruvate, and NADH, which are produced in the cytosol.<sup class="reference" id="cite_ref-Voet_5-2"><span>[</span>6<span>]</span></sup> This process of cellular respiration, also known as aerobic respiration, is dependent on the presence of oxygen. When oxygen is limited, the glycolytic products will be metabolized by anaerobic respiration, a process that is independent of the mitochondria.<sup class="reference" id="cite_ref-Voet_5-3"><span>[</span>6<span>]</span></sup> The production of ATP from glucose has an approximately 13-fold higher yield during aerobic respiration compared to anaerobic respiration.<sup class="reference" id="cite_ref-17"><span>[</span>18<span>]</span></sup></p>
+<p>&nbsp;</p>
+<h4><span class="mw-headline">Pyruvate: the citric acid cycle</span></h4>
+<dl><dd>
+<div class="noprint relarticle mainarticle">&nbsp;</div>
+</dd></dl>
+<p>Each pyruvate molecule produced by glycolysis is actively transported across the inner mitochondrial membrane, and into the matrix where it is oxidized and combined with coenzyme A to form CO<sub>2</sub>, acetyl-CoA, and NADH.<sup class="reference" id="cite_ref-Voet_5-4"><span>[</span>6<span>]</span></sup></p>
+<p>The acetyl-CoA is the primary substrate to enter the <em>citric acid cycle</em>, also known as the <em>tricarboxylic acid (TCA) cycle</em> or <em>Krebs cycle</em>. The enzymes of the citric acid cycle are located in the mitochondrial matrix, with the exception of succinate dehydrogenase, which is bound to the inner mitochondrial membrane as part of Complex II.<sup class="reference" id="cite_ref-18"><span>[</span>19<span>]</span></sup> The citric acid cycle oxidizes the acetyl-CoA to carbon dioxide, and, in the process, produces reduced cofactors (three molecules of NADH and one molecule of FADH<sub>2</sub>) that are a source of electrons for the <em>electron transport chain</em>, and a molecule of GTP (that is readily converted to an ATP).<sup class="reference" id="cite_ref-Voet_5-5"><span>[</span>6<span>]</span></sup></p>
+<p>&nbsp;</p>
+<h4><span class="mw-headline">NADH and FADH<sub>2</sub>: the electron transport chain</span> <dd></dd><br />
+[[미토콘드리아]]</h4>
+<div class="thumb tright">
+<div class="thumbinner" style="WIDTH: 302px">&nbsp;[[Image:Biological cell svg.png]]
+<div class="thumbcaption">Schematic of typical animal cell, showing subcellular components. Organelles:<br />
+(1) nucleolus<br />
+(2) nucleus<br />
+(3) ribosomes (little dots)<br />
+(4) vesicle<br />
+(5) rough endoplasmic reticulum (ER)<br />
+(6) Golgi apparatus<br />
+(7) Cytoskeleton<br />
+(8) smooth ER<br />
+(9) <strong class="selflink">mitochondria</strong><br />
+(10) vacuole<br />
+(11) cytoplasm<br />
+(12) lysosome<br />
+(13) centrioles within centrosome</div>
+</div>
+</div>
+<p>The redox energy from NADH and FADH<sub>2</sub> is transferred to oxygen (O<sub><small><font size="2">2</font></small></sub>) in several steps via the electron transport chain. These energy-rich molecules are produced within the matrix via the citric acid cycle but are also produced in the cytoplasm by glycolysis. Reducing equivalents from the cytoplasm can be imported via the malate-aspartate shuttle system of antiporter proteins or feed into the electron transport chain using a glycerol phosphate shuttle.<sup class="reference" id="cite_ref-Voet_5-6"><span>[</span>6<span>]</span></sup> Protein complexes in the inner membrane (NADH dehydrogenase, cytochrome c reductase, and cytochrome c oxidase) perform the transfer and the incremental release of energy is used to pump protons (H<sup>+</sup>) into the intermembrane space. This process is efficient, but a small percentage of electrons may prematurely reduce oxygen, forming reactive oxygen species such as superoxide.<sup class="reference" id="cite_ref-Voet_5-7"><span>[</span>6<span>]</span></sup> This can cause oxidative stress in the mitochondria and may contribute to the decline in mitochondrial function associated with the aging process.<sup class="reference" id="cite_ref-oxidativedamage_19-0"><span>[</span>20<span>]</span></sup></p>
+<p>As the proton concentration increases in the intermembrane space, a strong electrochemical gradient is established across the inner membrane. The protons can return to the matrix through the ATP synthase complex, and their potential energy is used to synthesize ATP from ADP and inorganic phosphate (P<sub>i</sub>).<sup class="reference" id="cite_ref-Voet_5-8"><span>[</span>6<span>]</span></sup> This process is called chemiosmosis, and was first described by Peter Mitchell<sup class="reference" id="cite_ref-Mitchella_20-0"><span>[</span>21<span>]</span></sup><sup class="reference" id="cite_ref-Mitchellb_21-0"><span>[</span>22<span>]</span></sup> who was awarded the 1978 Nobel Prize in Chemistry for his work. Later, part of the 1997 Nobel Prize in Chemistry was awarded to Paul D. Boyer and John E. Walker for their clarification of the working mechanism of ATP synthase.<sup class="reference" id="cite_ref-22"><span>[</span>23<span>]</span></sup></p>
+<p>&nbsp;</p>
+<h4><span class="mw-headline">Heat production</span></h4>
+<p>Under certain conditions, protons can re-enter the mitochondrial matrix without contributing to ATP synthesis. This process is known as <em>proton leak</em> or <em>mitochondrial uncoupling</em> and is due to the facilitated diffusion of protons into the matrix. The process results in the unharnessed potential energy of the proton electrochemical gradient being released as heat.<sup class="reference" id="cite_ref-Voet_5-9"><span>[</span>6<span>]</span></sup> The process is mediated by a proton channel called thermogenin, or UCP1.<sup class="reference" id="cite_ref-Mozo_23-0"><span>[</span>24<span>]</span></sup> Thermogenin is a 33kDa protein first discovered in 1973.<sup class="reference" id="cite_ref-Nicholls_24-0"><span>[</span>25<span>]</span></sup> Thermogenin is primarily found in brown adipose tissue, or brown fat, and is responsible for non-shivering thermogenesis. Brown adipose tissue is found in mammals, and is at its highest levels in early life and in hibernating animals. In humans, brown adipose tissue is present at birth and decreases with age.<sup class="reference" id="cite_ref-Mozo_23-1"><span>[</span>24<span>]</span></sup></p>
+<p>&nbsp;</p>
+<h3><span class="mw-headline">Storage of calcium ions</span></h3>
+<p>The concentrations of free calcium in the cell can regulate an array of reactions and is important for signal transduction in the cell. Mitochondria can transiently store calcium, a contributing process for the cell's homeostasis of calcium.<sup class="reference" id="cite_ref-Siegel_Basic_Neurochemistry_25-0"><span>[</span>26<span>]</span></sup> In fact, their ability to rapidly take in calcium for later release makes them very good &quot;cytosolic buffers&quot; for calcium.<sup class="reference" id="cite_ref-Rossier_26-0"><span>[</span>27<span>]</span></sup> The endoplasmic reticulum (ER) is the most significant storage site of calcium, and there is a significant interplay between the mitochondrion and ER with regard to calcium.<sup class="reference" id="cite_ref-27"><span>[</span>28<span>]</span></sup> The calcium is taken up into the matrix by a calcium uniporter on the inner mitochondrial membrane.<sup class="reference" id="cite_ref-MillerRJ_28-0"><span>[</span>29<span>]</span></sup> It is primarily driven by the mitochondrial membrane potential.<sup class="reference" id="cite_ref-Siegel_Basic_Neurochemistry_25-1"><span>[</span>26<span>]</span></sup> Release of this calcium back into the cell's interior can occur via a sodium-calcium exchange protein or via &quot;calcium-induced-calcium-release&quot; pathways.<sup class="reference" id="cite_ref-MillerRJ_28-1"><span>[</span>29<span>]</span></sup> This can initiate calcium spikes or calcium waves with large changes in the membrane potential. These can activate a series of second messenger system proteins that can coordinate processes such as neurotransmitter release in nerve cells and release of hormones in endocrine cells.</p>
+<p>&nbsp;</p>
+<h3><span class="mw-headline">Additional functions</span></h3>
+<p>Mitochondria play a central role in many other metabolic tasks, such as:</p>
 <ul>
-     <li>정의<br />-사립체, 미토콘드리아<br />-박테리아, 바이러스, 성숙적혈구를 제외한 모든 살아있는 세포안의 과립형 소기관<br /><br /></li>
+     <li>Regulation of the membrane potential<sup class="reference" id="cite_ref-Voet_5-10"><span>[</span>6<span>]</span></sup> </li>
-     <li>내용<br />-세포내 대사와 호흡기능을 한다.<br />-세포에 필요한 에너지를 ATP형태로 생성한다. </li>
+    <li>Apoptosis-programmed cell death<sup class="reference" id="cite_ref-29"><span>[</span>30<span>]</span></sup> </li>
+    <li>Glutamate-mediated excitotoxic neuronal injury<sup class="reference" id="cite_ref-30"><span>[</span>31<span>]</span></sup> </li>
+     <li>Cellular proliferation regulation<sup class="reference" id="cite_ref-McBride_31-0"><span>[</span>32<span>]</span></sup> </li>
+    <li>Regulation of cellular metabolism<sup class="reference" id="cite_ref-McBride_31-1"><span>[</span>32<span>]</span></sup> </li>
+    <li>Certain heme synthesis reactions<sup class="reference" id="cite_ref-32"><span>[</span>33<span>]</span></sup> <em>(see also: porphyrin)</em> </li>
+    <li>Steroid synthesis.<sup class="reference" id="cite_ref-Rossier_26-1"><span>[</span>27<span>]</span></sup> </li>
 </ul>
-<p> <a name="[문서의 처음]"></a></p>
+<p>Some mitochondrial functions are performed only in specific types of cells. For example, mitochondria in liver cells contain enzymes that allow them to detoxify ammonia, a waste product of protein metabolism. A mutation in the genes regulating any of these functions can result in mitochondrial diseases.</p>
-<p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">거의 모든 진핵세포에서 발견되는 미토콘드리아(mitochondria)는 종종 세포의 발전소로 일컬어진다. TCA회로의 활성과 전자전달과 산화적 인산화 과정에 의한 ATP합성이 미토콘드리아에서 일어난다. 투과전자현미경으로 보면 미토콘드리아는 대개 폭이 0.3~1.0 &mu;m, 길이가 5~10&mu;m인 원통형 구조이다. (이는 세균세포의 크기와 같다). 세포에는 보통 1,000개 이상의 미토콘드리아가 있지만 효모의 일부, 단세포 조류, 트리파나좀(trypanasome) 원생동물 등 몇 종에서는 하나의 거대한 관상 미토콘드리온이 세포질 전체에 퍼져있다.</span> </p>
+<p>&nbsp;</p>
-<p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">미토콘드리아는 이중막으로 둘러싸여 있으면 미토콘드리아의 외막과 내막 사이에는 6~8nm 정도의 공간이 있다.&nbsp; 내막은 주름이 많이 잡힌 크르스테(cristae, 단수는 crista)구조를 이루고 있어 막의 표면적이 매우 넓다. 크리스테 구조는 생물종마다 다르다. 진균류에서는 평판모양의 크리스테를 이루는 반면 유클레나와 같은 편모충류에서는 원반형을 이룬다. 관상 크리스테 또한 여러 종의 진핵세포에서 발견된다. 그러나 아메바에서는 소포형의 크리스테 구조를 한 미토콘드리아가 존재한다. 내막은 미토콘드리아의 기질을 둘러싸고 있다. 미토콘드리아 기질은 매우 조밀하며 리보좀과 DNA가 있고 때로는 커다란 인산칼슘 입자가 존재하기도 한다. 미토콘드리아에 있는 리보좀은 세포질에 있는 리보좀보다 작고 크기와 소단위의 구성성분 등 여러 면에서 세균의 것과 유사하다. 미토콘드리아 DNA는 세균의 DNA와 마찬가지로 환형 구조이다.</span> </p>
+<h2><span class="mw-headline">Origin</span></h2>
-<p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">미토콘드리아는 가 구획마다 존재하는 화학성분이나 효소의 종류가 다르다. 외막과 내막을 구성하는 지질의 조유도 다르다. 전자전달 및 산화적 인산화 과정에 관여하는 효소나 전자 수용체는 미토콘드리아의 내막에 존재한다. TCA 회로와 지방산의 &beta;-산화과정을 수행하는 효소는 미토콘드리아의 기질에 위치한다.</span> </p>
+<dl><dd>
-<p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">미토콘드리아의 내막에는 대략8.5nm인 작은 구형 입자가 안쪽 표면에 붙어있다. </span></p>
+<div class="noprint relarticle mainarticle">&nbsp;</div>
-<p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">이것이 F₁입자이며 세포내 호흡과정에서 ATP를 합성한다.</span> </p>
+</dd></dl>
-<p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">미토콘드리아에 있는 DNA와 리보좀은 미토콘드리아 DNA에 돌연변이가 일어나서 나타나는 질병도 있다. 그러나 대부분의 미토콘드리아 단백질 유전자는 핵 DNA에 존재한다. 미토콘드리아는 이분법에 의해 분열한다. 엽록체 역시 미토콘드리아와 마찬가지로 부분적인 독립성을 보이며 이분법으로 분열한다. 이들 세포소기관은 여러 측면에서 세균과 닮아 세균과 </span></p>
+<p>Mitochondria have many features in common with prokaryotes. As a result, they are believed to be originally derived from endosymbiotic prokaryotes.</p>
-<p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">커다란 세포사이의 공생관계에서 이러한 세포소기관이 형성되었다고 생각되고 있다.</span> </p>
+<p>A mitochondrion contains DNA, which is organized as several copies of a single, circular chromosome. This mitochondrial chromosome contains genes for ribosomes, and the twenty-one tRNA's necessary for the translation of messenger RNAs into protein. The circular structure is also found in prokaryotes, and the similarity is extended by the fact that mitochondrial DNA is organized with a variant genetic code similar to that of Proteobacteria.<sup class="reference" id="cite_ref-Shoulders1_33-0"><span>[</span>34<span>]</span></sup> This suggests that their ancestor, the so-called proto-mitochondrion, was a member of the Proteobacteria.<sup class="reference" id="cite_ref-Shoulders1_33-1"><span>[</span>34<span>]</span></sup> In particular, the proto-mitochondrion was probably related to the rickettsia.<sup class="reference" id="cite_ref-34"><span>[</span>35<span>]</span></sup> However, the exact relationship of the ancestor of mitochondria to the alpha-proteobacteria and whether the mitochondria was formed at the same time or after the nucleus, remains controversial.<sup class="reference" id="cite_ref-35"><span>[</span>36<span>]</span></sup></p>
-<p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><br /></span></p>
+<p>The ribosomes coded for by the mitochondrial DNA are similar to those from bacteria in size and structure.<sup class="reference" id="cite_ref-36"><span>[</span>37<span>]</span></sup> They closely resemble the bacterial 70S ribosome and not the 80S cytoplasmic ribosomes which are coded for by nuclear DNA.</p>
-<p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">☞미토콘드리아의 효소 분포</span> </p>
+<p>The endosymbiotic relationship of mitochondria with their host cells was popularized by Lynn Margulis.<sup class="reference" id="cite_ref-37"><span>[</span>38<span>]</span></sup> The endosymbiotic hypothesis suggests that mitochondria descended from bacteria that somehow survived endocytosis by another cell, and became incorporated into the cytoplasm. The ability of these bacteria to conduct respiration in host cells that had relied on glycolysis and fermentation would have provided a considerable evolutionary advantage. In a similar manner, host cells with symbiotic bacteria capable of photosynthesis would also have had an advantage. The incorporation of symbiotes would have increased the number of environments in which the cells could survive. This symbiotic relationship probably developed 1.7<sup class="reference" id="cite_ref-38"><span>[</span>39<span>]</span></sup>-2<sup class="reference" id="cite_ref-39"><span>[</span>40<span>]</span></sup> billion years ago.</p>
-<p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><a name="#4910c37d"></a></span>
+<p>A few groups of unicellular eukaryotes lack mitochondria: the microsporidians, metamonads, and archamoebae.<sup class="reference" id="cite_ref-Cavlier-Smith_40-0"><span>[</span>41<span>]</span></sup> These groups appear as the most primitive eukaryotes on phylogenetic trees constructed using rRNA information, suggesting that they appeared before the origin of mitochondria. However, this is now known to be an artifact of long-branch attraction &ndash; they are derived groups and retain genes or organelles derived from mitochondria (e.g., mitosomes and hydrogenosomes).<sup class="reference" id="cite_ref-mitosomes_0-1"><span>[</span>1<span>]</span></sup></p>
-<table style="BORDER-RIGHT: medium none; BORDER-TOP: medium none; BORDER-LEFT: medium none; BORDER-BOTTOM: medium none; BORDER-COLLAPSE: collapse" height="187" cellspacing="0" cellpadding="0" width="363" border="1">
+<p>&nbsp;</p>
+<h2><span class="mw-headline">Genome</span></h2>
+<dl><dd>
+<div class="noprint relarticle mainarticle">&nbsp;</div>
+</dd></dl>
+<p>The human mitochondrial genome is a circular DNA molecule of about 16&nbsp;kilobases.<sup class="reference" id="cite_ref-ChanDC_41-0"><span>[</span>42<span>]</span></sup> It encodes 37 genes: 13 for subunits of respiratory complexes I, III, IV and V, 22 for mitochondrial tRNA, and 2 for rRNA.<sup class="reference" id="cite_ref-ChanDC_41-1"><span>[</span>42<span>]</span></sup> One mitochondrion can contain two to ten copies of its DNA.<sup class="reference" id="cite_ref-Wiesner_42-0"><span>[</span>43<span>]</span></sup></p>
+<p>As in prokaryotes, there is a very high proportion of coding DNA and an absence of repeats. Mitochondrial genes are transcribed as multigenic transcripts, which are cleaved and polyadenylated to yield mature mRNAs. Not all proteins necessary for mitochondrial function are encoded by the mitochondrial genome; most are coded by genes in the cell nucleus and the corresponding proteins imported into the mitochondrion.<sup class="reference" id="cite_ref-Anderson_43-0"><span>[</span>44<span>]</span></sup> The exact number of genes encoded by the nucleus and the mitochondrial genome differs between species. In general, mitochondrial genomes are circular, although exceptions have been reported.<sup class="reference" id="cite_ref-Fukuhara_44-0"><span>[</span>45<span>]</span></sup> Also, in general, mitochondrial DNA lacks introns, as is the case in the human mitochondrial genome;<sup class="reference" id="cite_ref-Anderson_43-1"><span>[</span>44<span>]</span></sup> however, introns have been observed in some eukaryotic mitochondrial DNA,<sup class="reference" id="cite_ref-45"><span>[</span>46<span>]</span></sup> such as that of yeast<sup class="reference" id="cite_ref-46"><span>[</span>47<span>]</span></sup> and protists,<sup class="reference" id="cite_ref-47"><span>[</span>48<span>]</span></sup> including <em>Dictyostelium discoideum</em>.<sup class="reference" id="cite_ref-48"><span>[</span>49<span>]</span></sup></p>
+<p>While slight variations on the standard code had been predicted earlier,<sup class="reference" id="cite_ref-49"><span>[</span>50<span>]</span></sup> none was discovered until 1979, when researchers studying human mitochondrial genes determined that they used an alternative code.<sup class="reference" id="cite_ref-50"><span>[</span>51<span>]</span></sup> Many slight variants have been discovered since,<sup class="reference" id="cite_ref-51"><span>[</span>52<span>]</span></sup> including various alternative mitochondrial codes.<sup class="reference" id="cite_ref-52"><span>[</span>53<span>]</span></sup> Further, the AUA, AUC, and AUU codons are all allowable start codons.</p>
+<p>
+<table width="55%" align="center" class="wikitable">
+    <caption>Exceptions to the universal genetic code (UGC) in mitochondria<sup class="reference" id="cite_ref-Alberts_4-12"><span>[</span>5<span>]</span></sup></caption>
      <tbody>
          <tr>
-             <td style="BORDER-RIGHT: #000000 0.12mm solid; BORDER-TOP: #000000 0.12mm solid; BORDER-LEFT: #000000 0.12mm solid; BORDER-BOTTOM: #000000 0.12mm solid" valign="middle" width="80" height="36">
+             <th>Organism</th>
-            <p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">외막</span></p>
+             <th>Codon</th>
-             </td>
+             <th>Standard</th>
-            <td style="BORDER-RIGHT: #000000 0.12mm solid; BORDER-TOP: #000000 0.12mm solid; BORDER-LEFT: #000000 0.12mm solid; BORDER-BOTTOM: #000000 0.12mm solid" valign="middle" width="283" height="36">
+            <th>Novel</th>
-             <p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">모노아민 산화효소, 시트크롬 b5</span></p>
-            </td>
          </tr>
          <tr>
-             <td style="BORDER-RIGHT: #000000 0.12mm solid; BORDER-TOP: #000000 0.12mm solid; BORDER-LEFT: #000000 0.12mm solid; BORDER-BOTTOM: #000000 0.12mm solid" valign="middle" width="80" height="36">
+             <td rowspan="3">Mammalian</td>
-             <p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">막강공간</span></p>
+             <td>AGA,&nbsp;AGG</td>
-             </td>
+             <td>Arginine</td>
-            <td style="BORDER-RIGHT: #000000 0.12mm solid; BORDER-TOP: #000000 0.12mm solid; BORDER-LEFT: #000000 0.12mm solid; BORDER-BOTTOM: #000000 0.12mm solid" valign="middle" width="283" height="36">
+             <td>Stop&nbsp;codon</td>
-             <p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">아테닐산키나아제</span></p>
-            </td>
          </tr>
          <tr>
-             <td style="BORDER-RIGHT: #000000 0.12mm solid; BORDER-TOP: #000000 0.12mm solid; BORDER-LEFT: #000000 0.12mm solid; BORDER-BOTTOM: #000000 0.12mm solid" valign="middle" width="80" height="57">
+             <td>AUA</td>
-            <p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">내막</span></p>
+             <td>Isoleucine</td>
-            </td>
+             <td>Methionine</td>
-             <td style="BORDER-RIGHT: #000000 0.12mm solid; BORDER-TOP: #000000 0.12mm solid; BORDER-LEFT: #000000 0.12mm solid; BORDER-BOTTOM: #000000 0.12mm solid" valign="middle" width="283" height="57">
-            <p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">숙신산 탈수소효소. 시토크롬 산화효소, </span></p>
-             <p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">F₁- ATPase</span></p>
-            </td>
          </tr>
          <tr>
-             <td style="BORDER-RIGHT: #000000 0.12mm solid; BORDER-TOP: #000000 0.12mm solid; BORDER-LEFT: #000000 0.12mm solid; BORDER-BOTTOM: #000000 0.12mm solid" valign="middle" width="80" height="57">
+             <td>UGA</td>
-             <p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">기질</span></p>
+             <td>Stop&nbsp;codon</td>
-             </td>
+            <td>Tryptophan</td>
-             <td style="BORDER-RIGHT: #000000 0.12mm solid; BORDER-TOP: #000000 0.12mm solid; BORDER-LEFT: #000000 0.12mm solid; BORDER-BOTTOM: #000000 0.12mm solid" valign="middle" width="283" height="57">
+        </tr>
-             <p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">TCA 회로 효소계</span></p>
+        <tr>
-             <p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify">지방산 &beta;-산화효소계</span></p>
+            <td rowspan="3">Invertebrates</td>
-             </td>
+            <td>AGA, AGG</td>
+            <td>Arginine</td>
+            <td>Serine</td>
+        </tr>
+        <tr>
+            <td>AUA</td>
+            <td>Isoleucine</td>
+            <td>Methionine</td>
+        </tr>
+        <tr>
+            <td>UGA</td>
+             <td>Stop codon</td>
+             <td>Tryptophan</td>
+        </tr>
+        <tr>
+            <td rowspan="3">Yeast</td>
+            <td>AUA</td>
+            <td>Isoleucine</td>
+             <td>Methionine</td>
+        </tr>
+        <tr>
+            <td>UGA</td>
+            <td>Stop codon</td>
+             <td>Tryptophan</td>
+        </tr>
+        <tr>
+            <td>CUA</td>
+            <td>Leucine</td>
+             <td>Threonine</td>
          </tr>
      </tbody>
 </table>
-<span></span></p>
+</p>
-<p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;바탕&quot;; TEXT-ALIGN: justify"><br /></span></p>
+<p>Some of these differences should be regarded as pseudo-changes in the genetic code due to the phenomenon of RNA editing, which is common in mitochondria. In higher plants, it was thought that CGG encoded for tryptophan and not arginine; however, the codon in the processed RNA was discovered to be the UGG codon, consistent with the universal genetic code for tryptophan.<sup class="reference" id="cite_ref-53"><span>[</span>54<span>]</span></sup> Of note, the arthropod mitochondrial genetic code has undergone parallel evolution within a phylum, with some organisms uniquely translating AGG to lysine.<sup class="reference" id="cite_ref-54"><span>[</span>55<span>]</span></sup></p>
-<p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;한컴바탕&quot;; TEXT-ALIGN: justify"><span style="FONT-SIZE: 13px; COLOR: #000000; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;한컴바탕&quot;; TEXT-ALIGN: justify"><br /></span></p>
+<p>Mitochondrial genomes have far fewer genes than the bacteria from which they are thought to be descended. Although some have been lost altogether, many have been transferred to the nucleus, such as the respiratory complex II protein subunits.<sup class="reference" id="cite_ref-ChanDC_41-2"><span>[</span>42<span>]</span></sup> This is thought to be relatively common over evolutionary time. A few organisms, such as the <em>Cryptosporidium</em>, actually have mitochondria that lack any DNA, presumably because all their genes have been lost or transferred.<sup class="reference" id="cite_ref-Henriquez_55-0"><span>[</span>56<span>]</span></sup> In <em>Cryptosporidium</em>, the mitochondria have an altered ATP generation system that renders the parasite resistant to many classical mitochondrial inhibitors such as cyanide, azide, and atovaquone.<sup class="reference" id="cite_ref-Henriquez_55-1"><span>[</span>56<span>]</span></sup></p>
-<p style="FONT-SIZE: 13px; MARGIN: 0px; COLOR: #000000; TEXT-INDENT: 0px; LINE-HEIGHT: 21px; FONT-FAMILY: &quot;한컴바탕&quot;; TEXT-ALIGN: justify">&nbsp;</p>
+<p>&nbsp;</p>
+<h2><span class="mw-headline">Replication and inheritance</span></h2>
+<dl><dd></dd></dl>
+<p>Mitochondria divide by binary fission similar to bacterial cell division; unlike bacteria, however, mitochondria can also fuse with other mitochondria.<sup class="reference" id="cite_ref-ChanDC_41-3"><span>[</span>42<span>]</span></sup><sup class="reference" id="cite_ref-56"><span>[</span>57<span>]</span></sup>. The regulation of this division differs between eukaryotes. In many single-celled eukaryotes, their growth and division is linked to the cell cycle. For example, a single mitochondrion may divide synchronously with the nucleus. This division and segregation process must be tightly controlled so that each daughter cell receives at least one mitochondrion. In other eukaryotes (in humans for example), mitochondria may replicate their DNA and divide mainly in response to the energy needs of the cell, rather than in phase with the cell cycle. When the energy needs of a cell are high, mitochondria grow and divide. When the energy use is low, mitochondria are destroyed or become inactive. In such examples, and in contrast to the situation in many single celled eukaryotes, mitochondria are apparently randomly distributed to the daughter cells during the division of the cytoplasm.</p>
+<p>An individual's mitochondrial genes are not inherited by the same mechanism as nuclear genes. At fertilization of an egg cell by a sperm, the egg nucleus and sperm nucleus each contribute equally to the genetic makeup of the zygote nucleus. In contrast, the mitochondria, and therefore the mitochondrial DNA, usually comes from the egg only. The sperm's mitochondria enter the egg but does not contribute genetic information to the embryo.<sup class="reference" id="cite_ref-57"><span>[</span>58<span>]</span></sup> Instead, paternal mitochondria are marked with ubiquitin to select them for later destruction inside the embryo.<sup class="reference" id="cite_ref-58"><span>[</span>59<span>]</span></sup> The egg cell contains relatively few mitochondria, but it is these mitochondria that survive and divide to populate the cells of the adult organism. Mitochondria are, therefore, in most cases inherited down the female line, known as maternal inheritance. This mode is seen in most organisms including all animals. However, mitochondria in some species can sometimes be inherited paternally. This is the norm among certain coniferous plants, although not in pine trees and yew trees.<sup class="reference" id="cite_ref-59"><span>[</span>60<span>]</span></sup> It has also been suggested that it occurs at a very low level in humans.<sup class="reference" id="cite_ref-60"><span>[</span>61<span>]</span></sup></p>
+<p>Uniparental inheritance leads to little opportunity for genetic recombination between different lineages of mitochondria, although a single mitochondrion can contain 2&ndash;10 copies of its DNA.<sup class="reference" id="cite_ref-Wiesner_42-1"><span>[</span>43<span>]</span></sup> For this reason, mitochondrial DNA usually is thought to reproduce by binary fission. What recombination does take place maintains genetic integrity rather than maintaining diversity. However, there are studies showing evidence of recombination in mitochondrial DNA. It is clear that the enzymes necessary for recombination are present in mammalian cells.<sup class="reference" id="cite_ref-61"><span>[</span>62<span>]</span></sup> Further, evidence suggests that animal mitochondria can undergo recombination.<sup class="reference" id="cite_ref-62"><span>[</span>63<span>]</span></sup> The data are a bit more controversial in humans, although indirect evidence of recombination exists.<sup class="reference" id="cite_ref-63"><span>[</span>64<span>]</span></sup><sup class="reference" id="cite_ref-64"><span>[</span>65<span>]</span></sup> If recombination does not occur, the whole mitochondrial DNA sequence represents a single haplotype, which makes it useful for studying the evolutionary history of populations.</p>
+<p>&nbsp;</p>
+<h2><span class="mw-headline">Population genetic studies</span></h2>
+<dl><dd>
+<div class="noprint relarticle mainarticle">&nbsp;</div>
+</dd></dl>
+<p>The near-absence of genetic recombination in mitochondrial DNA makes it a useful source of information for scientists involved in population genetics and evolutionary biology.<sup class="reference" id="cite_ref-65"><span>[</span>66<span>]</span></sup> Because all the mitochondrial DNA is inherited as a single unit, or haplotype, the relationships between mitochondrial DNA from different individuals can be represented as a gene tree. Patterns in these gene trees can be used to infer the evolutionary history of populations. The classic example of this is in human evolutionary genetics, where the molecular clock can be used to provide a recent date for mitochondrial Eve.<sup class="reference" id="cite_ref-66"><span>[</span>67<span>]</span></sup><sup class="reference" id="cite_ref-67"><span>[</span>68<span>]</span></sup> This is often interpreted as strong support for a recent modern human expansion out of Africa.<sup class="reference" id="cite_ref-Garrigan06_68-0"><span>[</span>69<span>]</span></sup> Another human example is the sequencing of mitochondrial DNA from Neanderthal bones. The relatively-large evolutionary distance between the mitochondrial DNA sequences of Neanderthals and living humans has been interpreted as evidence for lack of interbreeding between Neanderthals and anatomically-modern humans.<sup class="reference" id="cite_ref-69"><span>[</span>70<span>]</span></sup></p>
+<p>However, mitochondrial DNA reflects the history of only females in a population and so may not represent the history of the population as a whole. This can be partially overcome by the use of paternal genetic sequences, such as the non-recombining region of the Y-chromosome.<sup class="reference" id="cite_ref-Garrigan06_68-1"><span>[</span>69<span>]</span></sup> In a broader sense, only studies that also include nuclear DNA can provide a comprehensive evolutionary history of a population.<sup class="reference" id="cite_ref-70"><span>[</span>71<span>]</span></sup></p>
+<p>&nbsp;</p>
+<h2><span class="mw-headline">Dysfunction and disease</span></h2>
+<p>&nbsp;</p>
+<h3><span class="mw-headline">Mitochondrial diseases</span></h3>
+<dl><dd>
+<div class="noprint relarticle mainarticle">&nbsp;</div>
+</dd></dl>
+<p>With their central place in cell metabolism, damage - and subsequent dysfunction - in mitochondria is an important factor in a wide range of human diseases. Mitochondrial disorders often present as neurological disorders, but can manifest as myopathy, diabetes, multiple endocrinopathy, or a variety of other systemic manifestations.<sup class="reference" id="cite_ref-Zeviani_71-0"><span>[</span>72<span>]</span></sup> Diseases caused by mutation in the mtDNA include Kearns-Sayre syndrome, MELAS syndrome and Leber's hereditary optic neuropathy.<sup class="reference" id="cite_ref-pmid15861210_72-0"><span>[</span>73<span>]</span></sup> In the vast majority of cases, these diseases are transmitted by a female to her children, as the zygote derives its mitochondria and hence its mtDNA from the ovum. Diseases such as Kearns-Sayre syndrome, Pearson's syndrome, and progressive external ophthalmoplegia are thought to be due to large-scale mtDNA rearrangements, whereas other diseases such as MELAS syndrome, Leber's hereditary optic neuropathy, myoclonic epilepsy with ragged red fibers (MERRF), and others are due to point mutations in mtDNA.<sup class="reference" id="cite_ref-Zeviani_71-1"><span>[</span>72<span>]</span></sup></p>
+<p>In other diseases, defects in nuclear genes lead to dysfunction of mitochondrial proteins. This is the case in Friedreich's ataxia, hereditary spastic paraplegia, and Wilson's disease.<sup class="reference" id="cite_ref-73"><span>[</span>74<span>]</span></sup> These diseases are inherited in a dominance relationship, as applies to most other genetic diseases. A variety of disorders can be caused by nuclear mutations of oxidative phosphorylation enzymes, such as coenzyme Q10 deficiency and Barth syndrome.<sup class="reference" id="cite_ref-Zeviani_71-2"><span>[</span>72<span>]</span></sup> Environmental influences may also interact with hereditary predispositions and cause mitochondrial disease. For example, there may be a link between pesticide exposure and the later onset of Parkinson's disease.<sup class="reference" id="cite_ref-74"><span>[</span>75<span>]</span></sup><sup class="reference" id="cite_ref-75"><span>[</span>76<span>]</span></sup></p>
+<p>Other diseases not directly linked to mitochondrial enzymes may feature dysfunction of mitochondria. These include schizophrenia, bipolar disorder, dementia, Alzheimer's disease, Parkinson's disease, epilepsy, stroke, cardiovascular disease, retinitis pigmentosa, and diabetes mellitus.<sup class="reference" id="cite_ref-76"><span>[</span>77<span>]</span></sup><sup class="reference" id="cite_ref-Pieczenik_77-0"><span>[</span>78<span>]</span></sup> The common thread linking these seemingly-unrelated conditions is cellular damage causing oxidative stress and the accumulation of reactive oxygen species. These oxidants then damage the mitochondrial DNA, resulting in mitochondrial dysfunction and cell death.<sup class="reference" id="cite_ref-Pieczenik_77-1"><span>[</span>78<span>]</span></sup></p>
+<p>&nbsp;</p>
+<h3><span class="mw-headline">Possible relationships to aging</span></h3>
+<p>Given the role of mitochondria as the cell's powerhouse, there may be some leakage of the high-energy electrons in the respiratory chain to form reactive oxygen species. This can result in significant oxidative stress in the mitochondria with high mutation rates of mitochondrial DNA.<sup class="reference" id="cite_ref-78"><span>[</span>79<span>]</span></sup> A vicious cycle is thought to occur, as oxidative stress leads to mitochondrial DNA mutations, which can lead to enzymatic abnormalities and further oxidative stress. A number of changes occur to mitochondria during the aging process.<sup class="reference" id="cite_ref-79"><span>[</span>80<span>]</span></sup> Tissues from elderly patients show a decrease in enzymatic activity of the proteins of the respiratory chain.<sup class="reference" id="cite_ref-80"><span>[</span>81<span>]</span></sup> Large deletions in the mitochondrial genome can lead to high levels of oxidative stress and neuronal death in Parkinson's disease.<sup class="reference" id="cite_ref-81"><span>[</span>82<span>]</span></sup> Hypothesized links between aging and oxidative stress are not new and were proposed over 50 years ago;<sup class="reference" id="cite_ref-82"><span>[</span>83<span>]</span></sup> however, there is much debate over whether mitochondrial changes are causes of aging or merely characteristics of aging. One notable study in mice demonstrated no increase in reactive oxygen species despite increasing mitochondrial DNA mutations, suggesting that the aging process is not due to oxidative stress.<sup class="reference" id="cite_ref-83"><span>[</span>84<span>]</span></sup> As a result, the exact relationships between mitochondria, oxidative stress, and aging have not yet been settled.</p>
+<p>&nbsp;</p>
+<h2><span class="mw-headline">References</span></h2>
+<div class="references-small references-column-count references-column-count-2" style="column-count: 2; -moz-column-count: 2">
+<ol class="references">
+    <li id="cite_note-mitosomes-0">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <cite class="Journal" id="CITEREFHenze_K.2C_Martin_W2003" style="FONT-STYLE: normal">Henze K, Martin W (2003). &quot;Evolutionary biology: essence of mitochondria&quot;. <em>Nature</em> <strong>426</strong> (6963): 127&ndash;8. doi:<span class="neverexpand">10.1038/426127a</span>. PMID 14614484.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Evolutionary+biology%3A+essence+of+mitochondria&amp;rft.jtitle=Nature&amp;rft.aulast=Henze+K%2C+Martin+W&amp;rft.au=Henze+K%2C+Martin+W&amp;rft.date=2003&amp;rft.volume=426&amp;rft.issue=6963&amp;rft.pages=127%26ndash%3B8&amp;rft_id=info:doi/10.1038%2F426127a&amp;rft_id=info:pmid/14614484&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-1"><strong>^</strong> <cite class="Journal" id="CITEREFMcBride_HM.2C_Neuspiel_M.2C_Wasiak_S2006" style="FONT-STYLE: normal">McBride HM, Neuspiel M, Wasiak S (2006). &quot;Mitochondria: more than just a powerhouse&quot;. <em>Curr. Biol.</em> <strong>16</strong> (14): R551. doi:<span class="neverexpand">10.1016/j.cub.2006.06.054</span>. PMID 16860735.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondria%3A+more+than+just+a+powerhouse&amp;rft.jtitle=Curr.+Biol.&amp;rft.aulast=McBride+HM%2C+Neuspiel+M%2C+Wasiak+S&amp;rft.au=McBride+HM%2C+Neuspiel+M%2C+Wasiak+S&amp;rft.date=2006&amp;rft.volume=16&amp;rft.issue=14&amp;rft.pages=R551&amp;rft_id=info:doi/10.1016%2Fj.cub.2006.06.054&amp;rft_id=info:pmid/16860735&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-2"><strong>^</strong> <cite class="Journal" id="CITEREFGardner_A.2C_Boles_RG2005" style="FONT-STYLE: normal">Gardner A, Boles RG (2005). &quot;Is a &quot;Mitochondrial Psychiatry&quot; in the Future? A Review&quot;. <em>Curr. Psychiatry Review</em> <strong>1</strong> (3): 255&ndash;271. doi:<span class="neverexpand">10.2174/157340005774575064</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Is+a+%22Mitochondrial+Psychiatry%22+in+the+Future%3F+A+Review&amp;rft.jtitle=Curr.+Psychiatry+Review&amp;rft.aulast=Gardner+A%2C+Boles+RG&amp;rft.au=Gardner+A%2C+Boles+RG&amp;rft.date=2005&amp;rft.volume=1&amp;rft.issue=3&amp;rft.pages=255%26ndash%3B271&amp;rft_id=info:doi/10.2174%2F157340005774575064&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-3"><strong>^</strong> <cite class="Journal" id="CITEREFLesnefsky_EJ.2C_et_al.2001" style="FONT-STYLE: normal">Lesnefsky EJ, et al. (2001). &quot;Mitochondrial dysfuntion in cardiac disease ischemia-reperfusion, aging and heart failure&quot;. <em>J. Mol. Cell. Cardiol.</em> <strong>33</strong> (6): 1065&ndash;1089. doi:<span class="neverexpand">10.1006/jmcc.2001.1378</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondrial+dysfuntion+in+cardiac+disease+ischemia-reperfusion%2C+aging+and+heart+failure&amp;rft.jtitle=J.+Mol.+Cell.+Cardiol.&amp;rft.aulast=Lesnefsky+EJ%2C+et+al.&amp;rft.au=Lesnefsky+EJ%2C+et+al.&amp;rft.date=2001&amp;rft.volume=33&amp;rft.issue=6&amp;rft.pages=1065%26ndash%3B1089&amp;rft_id=info:doi/10.1006%2Fjmcc.2001.1378&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Alberts-4">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <sup><em><strong>c</strong></em></sup> <sup><em><strong>d</strong></em></sup> <sup><em><strong>e</strong></em></sup> <sup><em><strong>f</strong></em></sup> <sup><em><strong>g</strong></em></sup> <sup><em><strong>h</strong></em></sup> <sup><em><strong>i</strong></em></sup> <sup><em><strong>j</strong></em></sup> <sup><em><strong>k</strong></em></sup> <sup><em><strong>l</strong></em></sup> <sup><em><strong>m</strong></em></sup> <cite class="book" id="Reference-Alberts-1994" style="FONT-STYLE: normal">Alberts, Bruce; Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter (1994). <em>Molecular Biology of the Cell</em>. New York: Garland Publishing Inc.. ISBN 0815332181.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=book&amp;rft.btitle=Molecular+Biology+of+the+Cell&amp;rft.aulast=Alberts&amp;rft.aufirst=Bruce&amp;rft.date=1994&amp;rft.pub=Garland+Publishing+Inc.&amp;rft.place=New+York&amp;rft.isbn=0815332181"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Voet-5">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <sup><em><strong>c</strong></em></sup> <sup><em><strong>d</strong></em></sup> <sup><em><strong>e</strong></em></sup> <sup><em><strong>f</strong></em></sup> <sup><em><strong>g</strong></em></sup> <sup><em><strong>h</strong></em></sup> <sup><em><strong>i</strong></em></sup> <sup><em><strong>j</strong></em></sup> <sup><em><strong>k</strong></em></sup> <cite class="book" id="Reference-Voet-2006" style="FONT-STYLE: normal">Voet, Donald; Judith G. Voet, Charlotte W. Pratt (2006). <em>Fundamentals of Biochemistry, 2nd Edition</em>. John Wiley and Sons, Inc., 547. ISBN 0471214957.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=book&amp;rft.btitle=Fundamentals+of+Biochemistry%2C+2nd+Edition&amp;rft.aulast=Voet&amp;rft.aufirst=Donald&amp;rft.date=2006&amp;rft.pub=John+Wiley+and+Sons%2C+Inc.&amp;rft.pages=547&amp;rft.isbn=0471214957"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-6"><strong>^</strong> <cite class="Journal" id="CITEREFTaylor_SW.2C_Fahy_E.2C_Zhang_B.2C_Glenn_GM.2C_Warnock_DE.2C_Wiley_S.2C_Murphy_AN.2C_Gaucher_SP.2C_Capaldi_RA.2C_Gibson_BW.2C_Ghosh_SS2003" style="FONT-STYLE: normal">Taylor SW, Fahy E, Zhang B, Glenn GM, Warnock DE, Wiley S, Murphy AN, Gaucher SP, Capaldi RA, Gibson BW, Ghosh SS (2003 March). &quot;Characterization of the human heart mitochondrial proteome&quot;. <em>Nat Biotechnol.</em> <strong>21</strong> (3): 281&ndash;6. doi:<span class="neverexpand">10.1038/nbt793</span>. PMID 12592411.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Characterization+of+the+human+heart+mitochondrial+proteome&amp;rft.jtitle=Nat+Biotechnol.&amp;rft.aulast=Taylor+SW%2C+Fahy+E%2C+Zhang+B%2C+Glenn+GM%2C+Warnock+DE%2C+Wiley+S%2C+Murphy+AN%2C+Gaucher+SP%2C+Capaldi+RA%2C+Gibson+BW%2C+Ghosh+SS&amp;rft.au=Taylor+SW%2C+Fahy+E%2C+Zhang+B%2C+Glenn+GM%2C+Warnock+DE%2C+Wiley+S%2C+Murphy+AN%2C+Gaucher+SP%2C+Capaldi+RA%2C+Gibson+BW%2C+Ghosh+SS&amp;rft.date=2003+March&amp;rft.volume=21&amp;rft.issue=3&amp;rft.pages=281%26ndash%3B6&amp;rft_id=info:doi/10.1038%2Fnbt793&amp;rft_id=info:pmid/12592411&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-7"><strong>^</strong> <cite class="Journal" id="CITEREFZhang_J.2C_Li_X.2C_Mueller_M.2C_Wang_Y.2C_Zong_C.2C_Deng_N.2C_Vondriska_TM.2C_Liem_DA.2C_Yang_J.2C_Korge_P.2C_Honda_H.2C_Weiss_JN.2C_Apweiler_R.2C_Ping_P2008" style="FONT-STYLE: normal">Zhang J, Li X, Mueller M, Wang Y, Zong C, Deng N, Vondriska TM, Liem DA, Yang J, Korge P, Honda H, Weiss JN, Apweiler R, Ping P (2008). &quot;Systematic characterization of the murine mitochondrial proteome using functionally validated cardiac mitochondira&quot;. <em>Proteomics</em> <strong>8</strong> (8): 1564&ndash;1575. doi:<span class="neverexpand">10.1002/pmic.200700851</span>. PMID 18348319.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Systematic+characterization+of+the+murine+mitochondrial+proteome+using+functionally+validated+cardiac+mitochondira&amp;rft.jtitle=Proteomics&amp;rft.aulast=Zhang+J%2C+Li+X%2C+Mueller+M%2C+Wang+Y%2C+Zong+C%2C+Deng+N%2C+Vondriska+TM%2C+Liem+DA%2C+Yang+J%2C+Korge+P%2C+Honda+H%2C+Weiss+JN%2C+Apweiler+R%2C+Ping+P&amp;rft.au=Zhang+J%2C+Li+X%2C+Mueller+M%2C+Wang+Y%2C+Zong+C%2C+Deng+N%2C+Vondriska+TM%2C+Liem+DA%2C+Yang+J%2C+Korge+P%2C+Honda+H%2C+Weiss+JN%2C+Apweiler+R%2C+Ping+P&amp;rft.date=2008&amp;rft.volume=8&amp;rft.issue=8&amp;rft.pages=1564%26ndash%3B1575&amp;rft_id=info:doi/10.1002%2Fpmic.200700851&amp;rft_id=info:pmid/18348319&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-8"><strong>^</strong> <cite class="Journal" id="CITEREFZhang_J.2C_Liem_DA.2C_Mueller_M.2C_Wang_Y.2C_Zong_C.2C_Deng_N.2C_Vondriska_TM.2C_Yang_J.2C_Korge_P.2C_Drews_O.2C_Maclellan_WR.2C_Honda_H.2C_Weiss_JN.2C_Apweiler_R.2C_Ping_P2008" style="FONT-STYLE: normal">Zhang J, Liem DA, Mueller M, Wang Y, Zong C, Deng N, Vondriska TM, Yang J, Korge P, Drews O, Maclellan WR, Honda H, Weiss JN, Apweiler R, Ping P (2008). &quot;Altered Proteome Biology of Cardiac Mitochondria Under Stress Conditions&quot;. <em>J. Proteome Res</em> <strong>7</strong>: 2204. doi:<span class="neverexpand">10.1021/pr070371f</span>. PMID 18484766.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Altered+Proteome+Biology+of+Cardiac+Mitochondria+Under+Stress+Conditions&amp;rft.jtitle=J.+Proteome+Res&amp;rft.aulast=Zhang+J%2C+Liem+DA%2C+Mueller+M%2C+Wang+Y%2C+Zong+C%2C+Deng+N%2C+Vondriska+TM%2C+Yang+J%2C+Korge+P%2C+Drews+O%2C+Maclellan+WR%2C+Honda+H%2C+Weiss+JN%2C+Apweiler+R%2C+Ping+P&amp;rft.au=Zhang+J%2C+Liem+DA%2C+Mueller+M%2C+Wang+Y%2C+Zong+C%2C+Deng+N%2C+Vondriska+TM%2C+Yang+J%2C+Korge+P%2C+Drews+O%2C+Maclellan+WR%2C+Honda+H%2C+Weiss+JN%2C+Apweiler+R%2C+Ping+P&amp;rft.date=2008&amp;rft.volume=7&amp;rft.pages=2204&amp;rft_id=info:doi/10.1021%2Fpr070371f&amp;rft_id=info:pmid/18484766&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-9"><strong>^</strong> <cite class="Journal" id="CITEREFAndersson_SG.2C_Karlberg_O.2C_Canb.C3.A4ck_B.2C_Kurland_CG2003" style="FONT-STYLE: normal">Andersson SG, Karlberg O, Canb&auml;ck B, Kurland CG (January 2003). &quot;On the origin of mitochondria: a genomics perspective&quot;. <em>Philos. Trans. R. Soc. Lond., B, Biol. Sci.</em> <strong>358</strong> (1429): 165&ndash;77; discussion 177&ndash;9. doi:<span class="neverexpand">10.1098/rstb.2002.1193</span>. PMID 12594925.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=On+the+origin+of+mitochondria%3A+a+genomics+perspective&amp;rft.jtitle=Philos.+Trans.+R.+Soc.+Lond.%2C+B%2C+Biol.+Sci.&amp;rft.aulast=Andersson+SG%2C+Karlberg+O%2C+Canb%C3%A4ck+B%2C+Kurland+CG&amp;rft.au=Andersson+SG%2C+Karlberg+O%2C+Canb%C3%A4ck+B%2C+Kurland+CG&amp;rft.date=January+2003&amp;rft.volume=358&amp;rft.issue=1429&amp;rft.pages=165%E2%80%9377%3B+discussion+177%E2%80%939&amp;rft_id=info:doi/10.1098%2Frstb.2002.1193&amp;rft_id=info:pmid/12594925&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Neupert-10">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <cite class="Journal" id="CITEREFHerrmann_JM.2C_Neupert_W2000" style="FONT-STYLE: normal">Herrmann JM, Neupert W (2000 April). &quot;Protein transport into mitochondria&quot;. <em>Curr Opin Microbiol</em> <strong>3</strong> (2): 210&ndash;214. doi:<span class="neverexpand">10.1016/S1369-5274(00)00077-1</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Protein+transport+into+mitochondria&amp;rft.jtitle=Curr+Opin+Microbiol&amp;rft.aulast=Herrmann+JM%2C+Neupert+W&amp;rft.au=Herrmann+JM%2C+Neupert+W&amp;rft.date=2000+April&amp;rft.volume=3&amp;rft.issue=2&amp;rft.pages=210%26ndash%3B214&amp;rft_id=info:doi/10.1016%2FS1369-5274%2800%2900077-1&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Chipuk-11">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <cite class="Journal" id="CITEREFChipuk_JE.2C_Bouchier-Hayes_L.2C_Green_DR2006" style="FONT-STYLE: normal">Chipuk JE, Bouchier-Hayes L, Green DR (2006). &quot;Mitochondrial outer membrane permeabilization during apoptosis: the innocent bystander scenario&quot;. <em>Cell Death and Differentiation.</em> <strong>13</strong>: 1396&ndash;1402. doi:<span class="neverexpand">10.1038/sj.cdd.4401963</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondrial+outer+membrane+permeabilization+during+apoptosis%3A+the+innocent+bystander+scenario&amp;rft.jtitle=Cell+Death+and+Differentiation.&amp;rft.aulast=Chipuk+JE%2C+Bouchier-Hayes+L%2C+Green+DR&amp;rft.au=Chipuk+JE%2C+Bouchier-Hayes+L%2C+Green+DR&amp;rft.date=2006&amp;rft.volume=13&amp;rft.pages=1396%26ndash%3B1402&amp;rft_id=info:doi/10.1038%2Fsj.cdd.4401963&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-McMillin-12"><strong>^</strong> <cite class="Journal" id="CITEREFMcMillin_JB.2C_Dowhan_W2002" style="FONT-STYLE: normal">McMillin JB, Dowhan W (2002 December). &quot;Cardiolipin and apoptosis&quot;. <em>Biochim. Et Biophys. Acta.</em> <strong>1585</strong>: 97&ndash;107. doi:<span class="neverexpand">10.1016/S1388-1981(02)00329-3</span>. PMID 12531542.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Cardiolipin+and+apoptosis&amp;rft.jtitle=Biochim.+Et+Biophys.+Acta.&amp;rft.aulast=McMillin+JB%2C+Dowhan+W&amp;rft.au=McMillin+JB%2C+Dowhan+W&amp;rft.date=2002+December&amp;rft.volume=1585&amp;rft.pages=97%26ndash%3B107&amp;rft_id=info:doi/10.1016%2FS1388-1981%2802%2900329-3&amp;rft_id=info:pmid/12531542&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Mannella-13"><strong>^</strong> <cite class="Journal" id="CITEREFMannella_CA2006" style="FONT-STYLE: normal">Mannella CA (2006). &quot;Structure and dynamics of the mitochondrial inner membrane cristae&quot;. <em>Biochimica et Biophysica Acta (BBA) - Mol Cell Res.</em> <strong>1763</strong> (5&ndash;6): 542&ndash;548. doi:<span class="neverexpand">10.1016/j.bbamcr.2006.04.006</span>. PMID 16730811.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Structure+and+dynamics+of+the+mitochondrial+inner+membrane+cristae&amp;rft.jtitle=Biochimica+et+Biophysica+Acta+%28BBA%29+-+Mol+Cell+Res.&amp;rft.aulast=Mannella+CA&amp;rft.au=Mannella+CA&amp;rft.date=2006&amp;rft.volume=1763&amp;rft.issue=5%26ndash%3B6&amp;rft.pages=542%26ndash%3B548&amp;rft_id=info:doi/10.1016%2Fj.bbamcr.2006.04.006&amp;rft_id=info:pmid/16730811&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-14"><strong>^</strong> <cite class="Journal" id="CITEREFAnderson_S.2C_Bankier_AT.2C_Barrell_BG.2C_de_Bruijn_MH.2C_Coulson_AR.2C_et_al.1981" style="FONT-STYLE: normal">Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, et al. (1981-04-09). &quot;Sequence and organization of the human mitochondrial genome&quot;. <em>Nature.</em> <strong>410</strong> (5806): 141. doi:<span class="neverexpand">10.1038/290457a0</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Sequence+and+organization+of+the+human+mitochondrial+genome&amp;rft.jtitle=Nature.&amp;rft.aulast=Anderson+S%2C+Bankier+AT%2C+Barrell+BG%2C+de+Bruijn+MH%2C+Coulson+AR%2C+et+al.&amp;rft.au=Anderson+S%2C+Bankier+AT%2C+Barrell+BG%2C+de+Bruijn+MH%2C+Coulson+AR%2C+et+al.&amp;rft.date=1981-04-09&amp;rft.volume=410&amp;rft.issue=5806&amp;rft.pages=141&amp;rft_id=info:doi/10.1038%2F290457a0&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-15"><strong>^</strong> <cite class="Journal" id="CITEREFRappaport_L.2C_Oliviero_P.2C_Samuel_JL1998" style="FONT-STYLE: normal">Rappaport L, Oliviero P, Samuel JL (1998). &quot;Cytoskeleton and mitochondrial morphology and function&quot;. <em>Mol and Cell Biochem.</em> <strong>184</strong>: 101&ndash;105. doi:<span class="neverexpand">10.1023/A:1006843113166</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Cytoskeleton+and+mitochondrial+morphology+and%0Afunction&amp;rft.jtitle=Mol+and+Cell+Biochem.&amp;rft.aulast=Rappaport+L%2C+Oliviero+P%2C+Samuel+JL&amp;rft.au=Rappaport+L%2C+Oliviero+P%2C+Samuel+JL&amp;rft.date=1998&amp;rft.volume=184&amp;rft.pages=101%26ndash%3B105&amp;rft_id=info:doi/10.1023%2FA%3A1006843113166&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-16"><strong>^</strong> <cite class="Journal" id="CITEREFTang_HL.2C_Lung_HL.2C_Wu_KC.2C_Le_AP.2C_Tang_HM.2C_Fung_MC2007" style="FONT-STYLE: normal">Tang HL, Lung HL, Wu KC, Le AP, Tang HM, Fung MC (2007). &quot;Vimentin supports mitochondrial morphology and organization&quot;. <em>Biochemical J</em> <strong>410</strong>: 141. doi:<span class="neverexpand">10.1042/BJ20071072</span>. PMID 17983357.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Vimentin+supports+mitochondrial+morphology+and+organization&amp;rft.jtitle=Biochemical+J&amp;rft.aulast=Tang+HL%2C+Lung+HL%2C+Wu+KC%2C+Le+AP%2C+Tang+HM%2C+Fung+MC&amp;rft.au=Tang+HL%2C+Lung+HL%2C+Wu+KC%2C+Le+AP%2C+Tang+HM%2C+Fung+MC&amp;rft.date=2007&amp;rft.volume=410&amp;rft.pages=141&amp;rft_id=info:doi/10.1042%2FBJ20071072&amp;rft_id=info:pmid/17983357&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-17"><strong>^</strong> <cite class="Journal" id="CITEREFRich_PR2003" style="FONT-STYLE: normal">Rich PR (2003). &quot;The molecular machinery of Keilin's respiratory chain&quot;. <em>Biochem. Soc. Trans.</em> <strong>31</strong> (Pt 6): 1095&ndash;105. PMID 14641005<span class="printonly">, http://www.biochemsoctrans.org/bst/031/1095/bst0311095.htm</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+molecular+machinery+of+Keilin%27s+respiratory+chain&amp;rft.jtitle=Biochem.+Soc.+Trans.&amp;rft.aulast=Rich+PR&amp;rft.au=Rich+PR&amp;rft.date=2003&amp;rft.volume=31&amp;rft.issue=Pt+6&amp;rft.pages=1095%26ndash%3B105&amp;rft_id=info:pmid/14641005&amp;rft_id=http%3A%2F%2Fwww.biochemsoctrans.org%2Fbst%2F031%2F1095%2Fbst0311095.htm&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-18"><strong>^</strong> <cite class="Journal" id="CITEREFKing_A.2C_Selak_MA.2C_Gottlieb_E2006" style="FONT-STYLE: normal">King A, Selak MA, Gottlieb E (2006). &quot;Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer&quot;. <em>Oncogene.</em> <strong>25</strong>: 4675&ndash;4682. doi:<span class="neverexpand">10.1038/sj.onc.1209594</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Succinate+dehydrogenase+and+fumarate+hydratase%3A+linking+mitochondrial+dysfunction+and+cancer&amp;rft.jtitle=Oncogene.&amp;rft.aulast=King+A%2C+Selak+MA%2C+Gottlieb+E&amp;rft.au=King+A%2C+Selak+MA%2C+Gottlieb+E&amp;rft.date=2006&amp;rft.volume=25&amp;rft.pages=4675%26ndash%3B4682&amp;rft_id=info:doi/10.1038%2Fsj.onc.1209594&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-oxidativedamage-19"><strong>^</strong> <cite class="Journal" id="CITEREFHuangK._G._Manton2004" style="FONT-STYLE: normal">Huang, K.; K. G. Manton (2004). &quot;The role of oxidative damage in mitochondria during aging: A review&quot;. <em>Frontiers in Bioscience</em> <strong>9</strong>: 1100&ndash;1117. doi:<span class="neverexpand">10.2741/1298</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+role+of+oxidative+damage+in+mitochondria+during+aging%3A+A+review&amp;rft.jtitle=Frontiers+in+Bioscience&amp;rft.aulast=Huang&amp;rft.aufirst=K.&amp;rft.au=Huang%2C+K.&amp;rft.au=K.+G.+Manton&amp;rft.date=2004&amp;rft.volume=9&amp;rft.pages=1100%26ndash%3B1117&amp;rft_id=info:doi/10.2741%2F1298&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Mitchella-20"><strong>^</strong> <cite class="Journal" id="CITEREFMitchell_P.2C_Moyle_J1967" style="FONT-STYLE: normal">Mitchell P, Moyle J (1967-01-14). &quot;Chemiosmotic hypothesis of oxidative phosphorylation&quot;. <em>Nature.</em> <strong>213</strong> (5072): 137&ndash;9. doi:<span class="neverexpand">10.1038/213137a0</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Chemiosmotic+hypothesis+of+oxidative+phosphorylation&amp;rft.jtitle=Nature.&amp;rft.aulast=Mitchell+P%2C+Moyle+J&amp;rft.au=Mitchell+P%2C+Moyle+J&amp;rft.date=1967-01-14&amp;rft.volume=213&amp;rft.issue=5072&amp;rft.pages=137%26ndash%3B9&amp;rft_id=info:doi/10.1038%2F213137a0&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Mitchellb-21"><strong>^</strong> <cite class="Journal" id="CITEREFMitchell_P1967" style="FONT-STYLE: normal">Mitchell P (1967-06-24). &quot;Proton current flow in mitochondrial systems&quot;. <em>Nature.</em> <strong>25</strong> (5095): 1327&ndash;8. doi:<span class="neverexpand">10.1038/2141327a0</span>. PMID 6056845.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Proton+current+flow+in+mitochondrial+systems&amp;rft.jtitle=Nature.&amp;rft.aulast=Mitchell+P&amp;rft.au=Mitchell+P&amp;rft.date=1967-06-24&amp;rft.volume=25&amp;rft.issue=5095&amp;rft.pages=1327%26ndash%3B8&amp;rft_id=info:doi/10.1038%2F2141327a0&amp;rft_id=info:pmid/6056845&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-22"><strong>^</strong> Nobel Foundation. &quot;Chemistry 1997&quot;. Retrieved on 2007-12-16. </li>
+    <li id="cite_note-Mozo-23">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <cite class="Journal" id="CITEREFMozo_J.2C_Emre_Y.2C_Bouillaud_F.2C_Ricquier_D.2C_Criscuolo_F2005" style="FONT-STYLE: normal">Mozo J, Emre Y, Bouillaud F, Ricquier D, Criscuolo F (2005 November). &quot;Thermoregulation: What Role for UCPs in Mammals and Birds?&quot;. <em>Bioscience Reports.</em> <strong>25</strong>: 227&ndash;249. doi:<span class="neverexpand">10.1007/s10540-005-2887-4</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Thermoregulation%3A+What+Role+for+UCPs+in+Mammals+and+Birds%3F&amp;rft.jtitle=Bioscience+Reports.&amp;rft.aulast=Mozo+J%2C+Emre+Y%2C+Bouillaud+F%2C+Ricquier+D%2C+Criscuolo+F&amp;rft.au=Mozo+J%2C+Emre+Y%2C+Bouillaud+F%2C+Ricquier+D%2C+Criscuolo+F&amp;rft.date=2005+November&amp;rft.volume=25&amp;rft.pages=227%26ndash%3B249&amp;rft_id=info:doi/10.1007%2Fs10540-005-2887-4&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Nicholls-24"><strong>^</strong> <cite class="Journal" id="CITEREFNicholls_DG.2C_Lindberg_O1973" style="FONT-STYLE: normal">Nicholls DG, Lindberg O (1973). &quot;Brown-adipose-tissue mitochondria. The influence of albumin and nucleotides on passive ion permeabilities&quot;. <em>Eur. J. Biochem.</em> <strong>37</strong>: R551. doi:<span class="neverexpand">10.1111/j.1432-1033.1973.tb03014.x</span>. PMID 4777251.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Brown-adipose-tissue+mitochondria.+The+influence+of+albumin+and+nucleotides+on+passive+ion+permeabilities&amp;rft.jtitle=Eur.+J.+Biochem.&amp;rft.aulast=Nicholls+DG%2C+Lindberg+O&amp;rft.au=Nicholls+DG%2C+Lindberg+O&amp;rft.date=1973&amp;rft.volume=37&amp;rft.pages=R551&amp;rft_id=info:doi/10.1111%2Fj.1432-1033.1973.tb03014.x&amp;rft_id=info:pmid/4777251&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Siegel_Basic_Neurochemistry-25">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <cite class="book" style="FONT-STYLE: normal">(1999) in Siegel GJ, Agranoff BW, Fisher SK, Albers RW, Uhler MD: <em>Basic Neurochemistry</em>, 6, Lippincott Williams &amp; Wilkins. ISBN 0-397-51820-X.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=book&amp;rft.btitle=Basic+Neurochemistry&amp;rft.date=1999&amp;rft.edition=6&amp;rft.pub=Lippincott+Williams+%26+Wilkins&amp;rft.isbn=0-397-51820-X"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Rossier-26">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <cite class="Journal" id="CITEREFRossier_MF2006" style="FONT-STYLE: normal">Rossier MF (2006). &quot;T channels and steroid biosynthesis: in search of a link with mitochondria&quot;. <em>Cell Calcium.</em> <strong>40</strong> (2): 155&ndash;64. doi:<span class="neverexpand">10.1016/j.ceca.2006.04.020</span>. PMID 16759697.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=T+channels+and+steroid+biosynthesis%3A+in+search+of+a+link+with+mitochondria&amp;rft.jtitle=Cell+Calcium.&amp;rft.aulast=Rossier+MF&amp;rft.au=Rossier+MF&amp;rft.date=2006&amp;rft.volume=40&amp;rft.issue=2&amp;rft.pages=155%E2%80%9364&amp;rft_id=info:doi/10.1016%2Fj.ceca.2006.04.020&amp;rft_id=info:pmid/16759697&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-27"><strong>^</strong> <cite class="Journal" id="CITEREFPizzo_P.2C_Pozzan_T2007" style="FONT-STYLE: normal">Pizzo P, Pozzan T (2007 October). &quot;Mitochondria&ndash;endoplasmic reticulum choreography: structure and signaling dynamics&quot;. <em>Trends Cell Bio.</em> <strong>17</strong> (10): 511&ndash;517. doi:<span class="neverexpand">10.1016/j.tcb.2007.07.011</span>. PMID 17851078.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondria%E2%80%93endoplasmic+reticulum+choreography%3A+structure+and+signaling+dynamics&amp;rft.jtitle=Trends+Cell+Bio.&amp;rft.aulast=Pizzo+P%2C+Pozzan+T&amp;rft.au=Pizzo+P%2C+Pozzan+T&amp;rft.date=2007+October&amp;rft.volume=17&amp;rft.issue=10&amp;rft.pages=511%E2%80%93517&amp;rft_id=info:doi/10.1016%2Fj.tcb.2007.07.011&amp;rft_id=info:pmid/17851078&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-MillerRJ-28">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <cite class="Journal" id="CITEREFMiller_RJ1998" style="FONT-STYLE: normal">Miller RJ (1998). &quot;Mitochondria &ndash; the kraken wakes!&quot;. <em>Trends in Neurosci.</em> <strong>21</strong> (3): 95&ndash;97 doi=10.1016/S0166&ndash;2236(97)01206&ndash;X. doi:<span class="neverexpand">10.1016/S0166-2236(97)01206-X</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondria+%E2%80%93+the+kraken+wakes%21&amp;rft.jtitle=Trends+in+Neurosci.&amp;rft.aulast=Miller+RJ&amp;rft.au=Miller+RJ&amp;rft.date=1998&amp;rft.volume=21&amp;rft.issue=3&amp;rft.pages=95%26ndash%3B97+doi%3D10.1016%2FS0166%E2%80%932236%2897%2901206%E2%80%93X&amp;rft_id=info:doi/10.1016%2FS0166-2236%2897%2901206-X&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-29"><strong>^</strong> <cite class="Journal" id="CITEREFGreen_DR1998" style="FONT-STYLE: normal">Green DR (1998 September). &quot;Apoptotic pathways: the roads to ruin&quot;. <em>Cell.</em> <strong>94</strong> (6): 695&ndash;8. doi:<span class="neverexpand">10.1016/S0092-8674(00)81728-6</span>. PMID 9753316.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Apoptotic+pathways%3A+the+roads+to+ruin&amp;rft.jtitle=Cell.&amp;rft.aulast=Green+DR&amp;rft.au=Green+DR&amp;rft.date=1998+September&amp;rft.volume=94&amp;rft.issue=6&amp;rft.pages=695%E2%80%938&amp;rft_id=info:doi/10.1016%2FS0092-8674%2800%2981728-6&amp;rft_id=info:pmid/9753316&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-30"><strong>^</strong> <cite class="Journal" id="CITEREFScanlon_JM.2C_Reynolds_IJ1998" style="FONT-STYLE: normal">Scanlon JM, Reynolds IJ (1998 December). &quot;Effects of oxidants and glutamate receptor activation on mitochondrial membrane potential in rat forebrain neurons&quot;. <em>J Neurochem.</em> <strong>71</strong> (6): 2392&ndash;400. doi:10.1046/j.1471-4159.1998.71062392.x (inactive 24 June 2008). PMID 9832137.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Effects+of+oxidants+and+glutamate+receptor+activation+on+mitochondrial+membrane+potential+in+rat+forebrain+neurons&amp;rft.jtitle=J+Neurochem.&amp;rft.aulast=Scanlon+JM%2C+Reynolds+IJ&amp;rft.au=Scanlon+JM%2C+Reynolds+IJ&amp;rft.date=1998+December&amp;rft.volume=71&amp;rft.issue=6&amp;rft.pages=2392%E2%80%93400&amp;rft_id=info:doi/10.1046%2Fj.1471-4159.1998.71062392.x&amp;rft_id=info:pmid/9832137&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-McBride-31">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <cite class="Journal" id="CITEREFMcBride_HM.2C_Neuspiel_M.2C_Wasiak_S2006" style="FONT-STYLE: normal">McBride HM, Neuspiel M, Wasiak S (2006 July). &quot;Mitochondria: more than just a powerhouse&quot;. <em>Curr Biol.</em> <strong>16</strong> (14): R551&ndash;60. doi:<span class="neverexpand">10.1016/j.cub.2006.06.054</span>. PMID 16860735.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondria%3A+more+than+just+a+powerhouse&amp;rft.jtitle=Curr+Biol.&amp;rft.aulast=McBride+HM%2C+Neuspiel+M%2C+Wasiak+S&amp;rft.au=McBride+HM%2C+Neuspiel+M%2C+Wasiak+S&amp;rft.date=2006+July&amp;rft.volume=16&amp;rft.issue=14&amp;rft.pages=R551%E2%80%9360&amp;rft_id=info:doi/10.1016%2Fj.cub.2006.06.054&amp;rft_id=info:pmid/16860735&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-32"><strong>^</strong> <cite class="Journal" id="CITEREFOh-hama_T1997" style="FONT-STYLE: normal">Oh-hama T (1997 August). &quot;Evolutionary consideration on 5-aminolevulinate synthase in nature&quot;. <em>Orig Life Evol Biosph.</em> <strong>27</strong> (4): 405&ndash;12. doi:<span class="neverexpand">10.1023/A:1006583601341</span>. PMID 9249985.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Evolutionary+consideration+on+5-aminolevulinate+synthase+in+nature&amp;rft.jtitle=Orig+Life+Evol+Biosph.&amp;rft.aulast=Oh-hama+T&amp;rft.au=Oh-hama+T&amp;rft.date=1997+August&amp;rft.volume=27&amp;rft.issue=4&amp;rft.pages=405%E2%80%9312&amp;rft_id=info:doi/10.1023%2FA%3A1006583601341&amp;rft_id=info:pmid/9249985&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Shoulders1-33">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <cite class="Journal" id="CITEREFFutuyma_DJ2005" style="FONT-STYLE: normal">Futuyma DJ (2005). &quot;On Darwin's Shoulders&quot;. <em>Natural History</em> <strong>114</strong> (9): 64&ndash;68.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=On+Darwin%27s+Shoulders&amp;rft.jtitle=Natural+History&amp;rft.aulast=Futuyma+DJ&amp;rft.au=Futuyma+DJ&amp;rft.date=2005&amp;rft.volume=114&amp;rft.issue=9&amp;rft.pages=64%26ndash%3B68&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-34"><strong>^</strong> <cite class="Journal" id="CITEREFEmelyanov_VV2003" style="FONT-STYLE: normal">Emelyanov VV (2003). &quot;Mitochondrial connection to the origin of the eukaryotic cell&quot;. <em>Eu J Biochem.</em> <strong>270</strong> (8): 1599&ndash;1618. doi:<span class="neverexpand">10.1046/j.1432-1033.2003.03499.x</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondrial+connection+to+the+origin+of+the+eukaryotic+cell&amp;rft.jtitle=Eu+J+Biochem.&amp;rft.aulast=Emelyanov+VV&amp;rft.au=Emelyanov+VV&amp;rft.date=2003&amp;rft.volume=270&amp;rft.issue=8&amp;rft.pages=1599%E2%80%931618&amp;rft_id=info:doi/10.1046%2Fj.1432-1033.2003.03499.x&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-35"><strong>^</strong> <cite class="Journal" id="CITEREFGray_MW.2C_Burger_G.2C_Lang_BF1999" style="FONT-STYLE: normal">Gray MW, Burger G, Lang BF (March 1999). &quot;Mitochondrial evolution&quot;. <em>Science (journal)</em> <strong>283</strong> (5407): 1476&ndash;81. PMID 10066161.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondrial+evolution&amp;rft.jtitle=Science+%28journal%29&amp;rft.aulast=Gray+MW%2C+Burger+G%2C+Lang+BF&amp;rft.au=Gray+MW%2C+Burger+G%2C+Lang+BF&amp;rft.date=March+1999&amp;rft.volume=283&amp;rft.issue=5407&amp;rft.pages=1476%E2%80%9381&amp;rft_id=info:pmid/10066161&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-36"><strong>^</strong> <cite class="Journal" id="CITEREFO.27Brien_TW2003" style="FONT-STYLE: normal">O'Brien TW (2003 September). &quot;Properties of human mitochondrial ribosomes&quot;. <em>IUBMB Life.</em> <strong>55</strong> (9): 505&ndash;13. doi:<span class="neverexpand">10.1080/15216540310001626610</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Properties+of+human+mitochondrial+ribosomes&amp;rft.jtitle=IUBMB+Life.&amp;rft.aulast=O%27Brien+TW&amp;rft.au=O%27Brien+TW&amp;rft.date=2003+September&amp;rft.volume=55&amp;rft.issue=9&amp;rft.pages=505%26ndash%3B13&amp;rft_id=info:doi/10.1080%2F15216540310001626610&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-37"><strong>^</strong> <cite class="Journal" id="CITEREFLynn_Sagan1967" style="FONT-STYLE: normal">Lynn Sagan (1967). &quot;On the origin of mitosing cells&quot;. <em>J Theor Bio.</em> <strong>14</strong> (3): 255&ndash;274. doi:<span class="neverexpand">10.1016/0022-5193(67)90079-3</span>. PMID 11541392.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=On+the+origin+of+mitosing+cells&amp;rft.jtitle=J+Theor+Bio.&amp;rft.aulast=Lynn+Sagan&amp;rft.au=Lynn+Sagan&amp;rft.date=1967&amp;rft.volume=14&amp;rft.issue=3&amp;rft.pages=255%E2%80%93274&amp;rft_id=info:doi/10.1016%2F0022-5193%2867%2990079-3&amp;rft_id=info:pmid/11541392&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-38"><strong>^</strong> <cite class="Journal" id="CITEREFEmelyanov_VV2001" style="FONT-STYLE: normal">Emelyanov VV (2001). &quot;Rickettsiaceae, rickettsia-like endosymbionts, and the origin of mitochondria&quot;. <em>Biosci. Rep.</em> <strong>21</strong>: 1&ndash;17. doi:<span class="neverexpand">10.1023/A:1010409415723</span>. PMID 11508688.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Rickettsiaceae%2C+rickettsia-like+endosymbionts%2C+and+the+origin+of+mitochondria&amp;rft.jtitle=Biosci.+Rep.&amp;rft.aulast=Emelyanov+VV&amp;rft.au=Emelyanov+VV&amp;rft.date=2001&amp;rft.volume=21&amp;rft.pages=1%E2%80%9317&amp;rft_id=info:doi/10.1023%2FA%3A1010409415723&amp;rft_id=info:pmid/11508688&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-39"><strong>^</strong> <cite class="Journal" id="CITEREFFeng_D-F.2C_Cho_G.2C_Doolittle_RF1997" style="FONT-STYLE: normal">Feng D-F, Cho G, Doolittle RF (1997). &quot;Determining divergence times with a protein clock: update and reevaluation&quot;. <em>Proc. Natl Acad. Sci.</em> <strong>94</strong>: 13028&ndash;13033. doi:<span class="neverexpand">10.1073/pnas.94.24.13028</span>. PMID 9371794.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Determining+divergence+times+with+a+protein+clock%3A+update+and+reevaluation&amp;rft.jtitle=Proc.+Natl+Acad.+Sci.&amp;rft.aulast=Feng+D-F%2C+Cho+G%2C+Doolittle+RF&amp;rft.au=Feng+D-F%2C+Cho+G%2C+Doolittle+RF&amp;rft.date=1997&amp;rft.volume=94&amp;rft.pages=13028%E2%80%9313033&amp;rft_id=info:doi/10.1073%2Fpnas.94.24.13028&amp;rft_id=info:pmid/9371794&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Cavlier-Smith-40"><strong>^</strong> <cite class="Journal" id="CITEREFCavalier-Smith_T1991" style="FONT-STYLE: normal">Cavalier-Smith T (1991). &quot;Archamoebae: the ancestral eukaryotes?&quot;. <em>Biosystems.</em> <strong>25</strong>: 1241. doi:<span class="neverexpand">10.1016/0303-2647(91)90010-I</span>. PMID 1854912.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Archamoebae%3A+the+ancestral+eukaryotes%3F&amp;rft.jtitle=Biosystems.&amp;rft.aulast=Cavalier-Smith+T&amp;rft.au=Cavalier-Smith+T&amp;rft.date=1991&amp;rft.volume=25&amp;rft.pages=1241&amp;rft_id=info:doi/10.1016%2F0303-2647%2891%2990010-I&amp;rft_id=info:pmid/1854912&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-ChanDC-41">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <sup><em><strong>c</strong></em></sup> <sup><em><strong>d</strong></em></sup> <cite class="Journal" id="CITEREFChan_DC2006" style="FONT-STYLE: normal">Chan DC (2006-06-30). &quot;Mitochondria: Dynamic Organelles in Disease, Aging, and Development&quot;. <em>Cell</em> <strong>125</strong> (7): 1241&ndash;1252. doi:<span class="neverexpand">10.1016/j.cell.2006.06.010</span>. PMID 16814712.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondria%3A+Dynamic+Organelles+in+Disease%2C+Aging%2C+and+Development&amp;rft.jtitle=Cell&amp;rft.aulast=Chan+DC&amp;rft.au=Chan+DC&amp;rft.date=2006-06-30&amp;rft.volume=125&amp;rft.issue=7&amp;rft.pages=1241%26ndash%3B1252&amp;rft_id=info:doi/10.1016%2Fj.cell.2006.06.010&amp;rft_id=info:pmid/16814712&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Wiesner-42">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <cite class="Journal" id="CITEREFWiesner_RJ.2C_Ruegg_JC.2C_Morano_I1992" style="FONT-STYLE: normal">Wiesner RJ, Ruegg JC, Morano I (1992). &quot;Counting target molecules by exponential polymerase chain reaction, copy number of mitochondrial DNA in rat tissues&quot;. <em>Biochim Biophys Acta</em> <strong>183</strong>: 553&ndash;559. PMID 1550563.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Counting+target+molecules+by+exponential+polymerase+chain+reaction%2C+copy+number+of+mitochondrial+DNA+in+rat+tissues&amp;rft.jtitle=Biochim+Biophys+Acta&amp;rft.aulast=Wiesner+RJ%2C+Ruegg+JC%2C+Morano+I&amp;rft.au=Wiesner+RJ%2C+Ruegg+JC%2C+Morano+I&amp;rft.date=1992&amp;rft.volume=183&amp;rft.pages=553%26ndash%3B559&amp;rft_id=info:pmid/1550563&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Anderson-43">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <cite class="Journal" id="CITEREFAnderson_S.2C_Bankier_AT.2C_Barrell_BG.2C_de-Bruijn_MHL.2C_Coulson_AR.2C_et_al.1981" style="FONT-STYLE: normal">Anderson S, Bankier AT, Barrell BG, de-Bruijn MHL, Coulson AR, et al. (1981). &quot;Sequence and organization of the human mitochondrial genome&quot;. <em>Nature</em> <strong>290</strong>: 427&ndash;465. doi:<span class="neverexpand">10.1038/290457a0</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Sequence+and+organization+of+the+human+mitochondrial+genome&amp;rft.jtitle=Nature&amp;rft.aulast=Anderson+S%2C+Bankier+AT%2C+Barrell+BG%2C+de-Bruijn+MHL%2C+Coulson+AR%2C+et+al.&amp;rft.au=Anderson+S%2C+Bankier+AT%2C+Barrell+BG%2C+de-Bruijn+MHL%2C+Coulson+AR%2C+et+al.&amp;rft.date=1981&amp;rft.volume=290&amp;rft.pages=427%26ndash%3B465&amp;rft_id=info:doi/10.1038%2F290457a0&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Fukuhara-44"><strong>^</strong> <cite class="Journal" id="CITEREFFukuhara_H.2C_Sor_F.2C_Drissi_R.2C_Dinou.C3.ABl_N.2C_Miyakawa_I.2C_Rousset.2C_and_Viola_AM1993" style="FONT-STYLE: normal">Fukuhara H, Sor F, Drissi R, Dinou&euml;l N, Miyakawa I, Rousset, and Viola AM (1993). &quot;Linear mitochondrial DNAs of yeasts: frequency of occurrence and general features&quot;. <em>Mol Cell Biol.</em> <strong>13</strong> (4): 2309&ndash;2314. PMID 8455612.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Linear+mitochondrial+DNAs+of+yeasts%3A+frequency+of+occurrence+and+general+features&amp;rft.jtitle=Mol+Cell+Biol.&amp;rft.aulast=Fukuhara+H%2C+Sor+F%2C+Drissi+R%2C+Dinou%C3%ABl+N%2C+Miyakawa+I%2C+Rousset%2C+and+Viola+AM&amp;rft.au=Fukuhara+H%2C+Sor+F%2C+Drissi+R%2C+Dinou%C3%ABl+N%2C+Miyakawa+I%2C+Rousset%2C+and+Viola+AM&amp;rft.date=1993&amp;rft.volume=13&amp;rft.issue=4&amp;rft.pages=2309%26ndash%3B2314&amp;rft_id=info:pmid/8455612&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-45"><strong>^</strong> <cite class="Journal" id="CITEREFBernardi_G1978" style="FONT-STYLE: normal">Bernardi G (1978). &quot;Intervening sequences in the mitochondrial genome&quot;. <em>Nature.</em> <strong>276</strong> (5688): 558&ndash;559. doi:<span class="neverexpand">10.1038/276558a0</span>. PMID 214710.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Intervening+sequences+in+the+mitochondrial+genome&amp;rft.jtitle=Nature.&amp;rft.aulast=Bernardi+G&amp;rft.au=Bernardi+G&amp;rft.date=1978&amp;rft.volume=276&amp;rft.issue=5688&amp;rft.pages=558%26ndash%3B559&amp;rft_id=info:doi/10.1038%2F276558a0&amp;rft_id=info:pmid/214710&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-46"><strong>^</strong> <cite class="Journal" id="CITEREFHebbar_SK.2C_Belcher_SM.2C_Perlman_PS1992" style="FONT-STYLE: normal">Hebbar SK, Belcher SM, Perlman PS (1992 April). &quot;A maturase-encoding group IIA intron of yeast mitochondria self-splices in vitro&quot;. <em>Nucleic Acids Res.</em> <strong>20</strong> (7): 1747&ndash;54. doi:<span class="neverexpand">10.1093/nar/20.7.1747</span>. PMID 1579468.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=A+maturase-encoding+group+IIA+intron+of+yeast+mitochondria+self-splices+in+vitro&amp;rft.jtitle=Nucleic+Acids+Res.&amp;rft.aulast=Hebbar+SK%2C+Belcher+SM%2C+Perlman+PS&amp;rft.au=Hebbar+SK%2C+Belcher+SM%2C+Perlman+PS&amp;rft.date=1992+April&amp;rft.volume=20&amp;rft.issue=7&amp;rft.pages=1747%26ndash%3B54&amp;rft_id=info:doi/10.1093%2Fnar%2F20.7.1747&amp;rft_id=info:pmid/1579468&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-47"><strong>^</strong> <cite class="Journal" id="CITEREFGray_MW.2C_Lang_BF.2C_Cedergren_R.2C_Golding_GB.2C_Lemieux_C.2C_Sankoff_D.2C_et_al1998" style="FONT-STYLE: normal">Gray MW, Lang BF, Cedergren R, Golding GB, Lemieux C, Sankoff D, et al (1998). &quot;Genome structure and gene content in protist mitochondrial DNAs&quot;. <em>Nucl Acids Res.</em> <strong>26</strong> (4): 865&ndash;878. doi:<span class="neverexpand">10.1093/nar/26.4.865</span>. PMID 9461442.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Genome+structure+and+gene+content+in+protist+mitochondrial+DNAs&amp;rft.jtitle=Nucl+Acids+Res.&amp;rft.aulast=Gray+MW%2C+Lang+BF%2C+Cedergren+R%2C+Golding+GB%2C+Lemieux+C%2C+Sankoff+D%2C+et+al&amp;rft.au=Gray+MW%2C+Lang+BF%2C+Cedergren+R%2C+Golding+GB%2C+Lemieux+C%2C+Sankoff+D%2C+et+al&amp;rft.date=1998&amp;rft.volume=26&amp;rft.issue=4&amp;rft.pages=865%26ndash%3B878&amp;rft_id=info:doi/10.1093%2Fnar%2F26.4.865&amp;rft_id=info:pmid/9461442&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-48"><strong>^</strong> <cite class="Journal" id="CITEREFGray_MW.2C_Lang_BF.2C_Burger_G2004" style="FONT-STYLE: normal">Gray MW, Lang BF, Burger G (2004). &quot;Mitochondria of protists&quot;. <em>Ann Rev of Genetics.</em> <strong>38</strong>: 477&ndash;524. doi:<span class="neverexpand">10.1146/annurev.genet.37.110801.142526</span>. PMID 15568984.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondria+of+protists&amp;rft.jtitle=Ann+Rev+of+Genetics.&amp;rft.aulast=Gray+MW%2C+Lang+BF%2C+Burger+G&amp;rft.au=Gray+MW%2C+Lang+BF%2C+Burger+G&amp;rft.date=2004&amp;rft.volume=38&amp;rft.pages=477%26ndash%3B524&amp;rft_id=info:doi/10.1146%2Fannurev.genet.37.110801.142526&amp;rft_id=info:pmid/15568984&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-49"><strong>^</strong> Crick, F. H. C. and Orgel, L. E. (1973) &quot;Directed panspermia.&quot; Icarus 19:341-346. p. 344: &quot;It is a little surprising that organisms with somewhat different codes do not coexist.&quot; (Further discussion at [1]) </li>
+    <li id="cite_note-50"><strong>^</strong> <cite class="Journal" id="CITEREFBarrell_BG.2C_Bankier_AT.2C_Drouin_J1979" style="FONT-STYLE: normal">Barrell BG, Bankier AT, Drouin J (1979). &quot;A different genetic code in human mitochondria&quot;. <em>Nature.</em> <strong>282</strong>: 189&ndash;194. doi:<span class="neverexpand">10.1038/282189a0</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=A+different+genetic+code+in+human+mitochondria&amp;rft.jtitle=Nature.&amp;rft.aulast=Barrell+BG%2C+Bankier+AT%2C+Drouin+J&amp;rft.au=Barrell+BG%2C+Bankier+AT%2C+Drouin+J&amp;rft.date=1979&amp;rft.volume=282&amp;rft.pages=189%26ndash%3B194&amp;rft_id=info:doi/10.1038%2F282189a0&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-51"><strong>^</strong> NCBI: &quot;The Genetic Codes&quot;, Compiled by Andrzej (Anjay) Elzanowski and Jim Ostell </li>
+    <li id="cite_note-52"><strong>^</strong> <cite class="Journal" id="CITEREFJukes_TH.2C_Osawa_S1990" style="FONT-STYLE: normal">Jukes TH, Osawa S (1990-12-01). &quot;The genetic code in mitochondria and chloroplasts&quot;. <em>Experientia.</em> <strong>46</strong> (11&ndash;12): 1117&ndash;26. doi:<span class="neverexpand">10.1007/BF01936921</span>. PMID 2253709.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+genetic+code+in+mitochondria+and+chloroplasts&amp;rft.jtitle=Experientia.&amp;rft.aulast=Jukes+TH%2C+Osawa+S&amp;rft.au=Jukes+TH%2C+Osawa+S&amp;rft.date=1990-12-01&amp;rft.volume=46&amp;rft.issue=11%26ndash%3B12&amp;rft.pages=1117%26ndash%3B26&amp;rft_id=info:doi/10.1007%2FBF01936921&amp;rft_id=info:pmid/2253709&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-53"><strong>^</strong> <cite class="Journal" id="CITEREFHiesel_R.2C_Wissinger_B.2C_Schuster_W.2C_Brennicke_A2006" style="FONT-STYLE: normal">Hiesel R, Wissinger B, Schuster W, Brennicke A (2006). &quot;RNA editing in plant mitochondria&quot;. <em>Science.</em> <strong>246</strong> (4937): 1632&ndash;4. doi:<span class="neverexpand">10.1126/science.2480644</span>. PMID 2480644.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=RNA+editing+in+plant+mitochondria&amp;rft.jtitle=Science.&amp;rft.aulast=Hiesel+R%2C+Wissinger+B%2C+Schuster+W%2C+Brennicke+A&amp;rft.au=Hiesel+R%2C+Wissinger+B%2C+Schuster+W%2C+Brennicke+A&amp;rft.date=2006&amp;rft.volume=246&amp;rft.issue=4937&amp;rft.pages=1632%26ndash%3B4&amp;rft_id=info:doi/10.1126%2Fscience.2480644&amp;rft_id=info:pmid/2480644&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-54"><strong>^</strong> <cite class="Journal" id="CITEREFAbascal_F.2C_Posada_D.2C_Knight_RD.2C_Zardoya_R2006" style="FONT-STYLE: normal">Abascal F, Posada D, Knight RD, Zardoya R (2006). &quot;Parallel Evolution of the Genetic Code in Arthropod Mitochondrial Genomes&quot;. <em>PLoS Biology.</em> <strong>4</strong> (5): 0711&ndash;0718. doi:<span class="neverexpand">10.1371/journal.pbio.0040127</span>. PMID 16620150.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Parallel+Evolution+of+the+Genetic+Code+in+Arthropod+Mitochondrial+Genomes&amp;rft.jtitle=PLoS+Biology.&amp;rft.aulast=Abascal+F%2C+Posada+D%2C+Knight+RD%2C+Zardoya+R&amp;rft.au=Abascal+F%2C+Posada+D%2C+Knight+RD%2C+Zardoya+R&amp;rft.date=2006&amp;rft.volume=4&amp;rft.issue=5&amp;rft.pages=0711%26ndash%3B0718&amp;rft_id=info:doi/10.1371%2Fjournal.pbio.0040127&amp;rft_id=info:pmid/16620150&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Henriquez-55">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <cite class="Journal" id="CITEREFHenriquez_FL.2C_Richards_TA.2C_Roberts_F.2C_McLeod_R.2C_Roberts_CW2005" style="FONT-STYLE: normal">Henriquez FL, Richards TA, Roberts F, McLeod R, Roberts CW (2005 February). &quot;The unusual mitochondrial compartment of Cryptosporidium parvum&quot;. <em>Trends Parasitol.</em> <strong>21</strong> (2): 68&ndash;74. doi:<span class="neverexpand">10.1016/j.pt.2004.11.010</span>. PMID 15664529.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+unusual+mitochondrial+compartment+of+Cryptosporidium+parvum&amp;rft.jtitle=Trends+Parasitol.&amp;rft.aulast=Henriquez+FL%2C+Richards+TA%2C+Roberts+F%2C+McLeod+R%2C+Roberts+CW&amp;rft.au=Henriquez+FL%2C+Richards+TA%2C+Roberts+F%2C+McLeod+R%2C+Roberts+CW&amp;rft.date=2005+February&amp;rft.volume=21&amp;rft.issue=2&amp;rft.pages=68%26ndash%3B74&amp;rft_id=info:doi/10.1016%2Fj.pt.2004.11.010&amp;rft_id=info:pmid/15664529&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-56"><strong>^</strong> <cite class="Journal" id="CITEREFHermann_GJ.2C_Thatcher_JW.2C_Mills_JP.2C_Hales_KG.2C_Fuller_MT.2C_Nunnari_J.2C_Shaw_JM1998" style="FONT-STYLE: normal">Hermann GJ, Thatcher JW, Mills JP, Hales KG, Fuller MT, Nunnari J, Shaw JM (1998 October). &quot;Mitochondrial Fusion in Yeast Requires the Transmembrane GTPase Fzo1p&quot;. <em>J. Cell. Bio.</em> <strong>143</strong> (2): 359&ndash;373. doi:<span class="neverexpand">10.1083/jcb.143.2.359</span>. PMID 9786948.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondrial+Fusion+in+Yeast+Requires+the+Transmembrane+GTPase+Fzo1p&amp;rft.jtitle=J.+Cell.+Bio.&amp;rft.aulast=Hermann+GJ%2C+Thatcher+JW%2C+Mills+JP%2C+Hales+KG%2C+Fuller+MT%2C+Nunnari+J%2C+Shaw+JM&amp;rft.au=Hermann+GJ%2C+Thatcher+JW%2C+Mills+JP%2C+Hales+KG%2C+Fuller+MT%2C+Nunnari+J%2C+Shaw+JM&amp;rft.date=1998+October&amp;rft.volume=143&amp;rft.issue=2&amp;rft.pages=359%26ndash%3B373&amp;rft_id=info:doi/10.1083%2Fjcb.143.2.359&amp;rft_id=info:pmid/9786948&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-57"><strong>^</strong> Kimball, J.W. (2006) &quot;Sexual Reproduction in Humans: Copulation and Fertilization,&quot; <em>Kimball's Biology Pages</em> (based on <em>Biology</em>, 6th ed., 1996)] </li>
+    <li id="cite_note-58"><strong>^</strong> <cite class="Journal" id="CITEREFSutovsky.2C_P..2C_et._al1999" style="FONT-STYLE: normal">Sutovsky, P., et. al (1999). &quot;Ubiquitin tag for sperm mitochondria&quot;. <em>Nature</em> <strong>402</strong>: 371&ndash;372. doi:<span class="neverexpand">10.1038/46466</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Ubiquitin+tag+for+sperm+mitochondria&amp;rft.jtitle=%5B%5BNature+%28journal%29%7CNature%5D%5D&amp;rft.aulast=Sutovsky%2C+P.%2C+et.+al&amp;rft.au=Sutovsky%2C+P.%2C+et.+al&amp;rft.date=1999&amp;rft.volume=402&amp;rft.pages=371%26ndash%3B372&amp;rft_id=info:doi/10.1038%2F46466&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> Discussed in <em>Science News</em>. </li>
+    <li id="cite_note-59"><strong>^</strong> <cite class="Journal" id="CITEREFMogensen_HL1996" style="FONT-STYLE: normal">Mogensen HL (1996). &quot;The Hows and Whys of Cytoplasmic Inheritance in Seed Plants&quot;. <em>American Journal of Botany</em> <strong>83</strong>: 247. doi:<span class="neverexpand">10.2307/2446172</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+Hows+and+Whys+of+Cytoplasmic+Inheritance+in+Seed+Plants&amp;rft.jtitle=American+Journal+of+Botany&amp;rft.aulast=Mogensen+HL&amp;rft.au=Mogensen+HL&amp;rft.date=1996&amp;rft.volume=83&amp;rft.pages=247&amp;rft_id=info:doi/10.2307%2F2446172&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-60"><strong>^</strong> <cite class="Journal" id="CITEREFJohns2003" style="FONT-STYLE: normal">Johns, D. R. (2003). &quot;Paternal transmission of mitochondrial DNA is (fortunately) rare&quot;. <em>Annals of Neurology</em> <strong>54</strong>: 422&ndash;4. doi:<span class="neverexpand">10.1002/ana.10771</span>. PMID 14520651.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Paternal+transmission+of+mitochondrial+DNA+is+%28fortunately%29+rare&amp;rft.jtitle=Annals+of+Neurology&amp;rft.aulast=Johns&amp;rft.aufirst=D.+R.&amp;rft.au=Johns%2C+D.+R.&amp;rft.date=2003&amp;rft.volume=54&amp;rft.pages=422%26ndash%3B4&amp;rft_id=info:doi/10.1002%2Fana.10771&amp;rft_id=info:pmid/14520651&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-61"><strong>^</strong> <cite class="Journal" id="CITEREFThyagarajan_B.2C_Padua_RA.2C_Campbell_C1996" style="FONT-STYLE: normal">Thyagarajan B, Padua RA, Campbell C (1996). &quot;Mammalian mitochondria possess homologous DNA recombination activity&quot;. <em>J. Biol. Chem.</em> <strong>271</strong> (44): 27536&ndash;27543. doi:<span class="neverexpand">10.1074/jbc.271.44.27536</span>. PMID 8910339.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mammalian+mitochondria+possess+homologous+DNA+recombination+activity&amp;rft.jtitle=J.+Biol.+Chem.&amp;rft.aulast=Thyagarajan+B%2C+Padua+RA%2C+Campbell+C&amp;rft.au=Thyagarajan+B%2C+Padua+RA%2C+Campbell+C&amp;rft.date=1996&amp;rft.volume=271&amp;rft.issue=44&amp;rft.pages=27536%26ndash%3B27543&amp;rft_id=info:doi/10.1074%2Fjbc.271.44.27536&amp;rft_id=info:pmid/8910339&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-62"><strong>^</strong> <cite class="Journal" id="CITEREFLunt_DB.2C_Hyman_BC1997" style="FONT-STYLE: normal">Lunt DB, Hyman BC (15 May 1997). &quot;Animal mitochondrial DNA recombination&quot;. <em>Nature</em> <strong>387</strong>: 247. doi:<span class="neverexpand">10.1038/387247a0</span>. PMID 9153388.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Animal+mitochondrial+DNA+recombination&amp;rft.jtitle=Nature&amp;rft.aulast=Lunt+DB%2C+Hyman+BC&amp;rft.au=Lunt+DB%2C+Hyman+BC&amp;rft.date=15+May+1997&amp;rft.volume=387&amp;rft.pages=247&amp;rft_id=info:doi/10.1038%2F387247a0&amp;rft_id=info:pmid/9153388&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-63"><strong>^</strong> <cite class="Journal" id="CITEREFEyre-Walker_A.2C_Smith_NH.2C_Maynard_Smith_J1999" style="FONT-STYLE: normal">Eyre-Walker A, Smith NH, Maynard Smith J (1999-03-07). &quot;How clonal are human mitochondria?&quot;. <em>Proc. Royal Soc. Biol. Sci. (Series B)</em> <strong>266</strong> (1418): 477&ndash;483. doi:<span class="neverexpand">10.1098/rspb.1999.0662</span>. PMID 10189711.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=How+clonal+are+human+mitochondria%3F&amp;rft.jtitle=Proc.+Royal+Soc.+Biol.+Sci.+%28Series+B%29&amp;rft.aulast=Eyre-Walker+A%2C+Smith+NH%2C+Maynard+Smith+J&amp;rft.au=Eyre-Walker+A%2C+Smith+NH%2C+Maynard+Smith+J&amp;rft.date=1999-03-07&amp;rft.volume=266&amp;rft.issue=1418&amp;rft.pages=477%26ndash%3B483&amp;rft_id=info:doi/10.1098%2Frspb.1999.0662&amp;rft_id=info:pmid/10189711&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-64"><strong>^</strong> <cite class="Journal" id="CITEREFAwadalla_P.2C_Eyre-Walker_A.2C_Maynard_Smith_J1999" style="FONT-STYLE: normal">Awadalla P, Eyre-Walker A, Maynard Smith J (24 December 1999). &quot;Linkage Disequilibrium and Recombination in Hominid Mitochondrial DNA&quot;. <em>Science.</em> <strong>286</strong> (5449): 2524&ndash;2525. doi:<span class="neverexpand">10.1126/science.286.5449.2524</span>. PMID 10617471.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Linkage+Disequilibrium+and+Recombination+in+Hominid+Mitochondrial+DNA&amp;rft.jtitle=Science.&amp;rft.aulast=Awadalla+P%2C+Eyre-Walker+A%2C+Maynard+Smith+J&amp;rft.au=Awadalla+P%2C+Eyre-Walker+A%2C+Maynard+Smith+J&amp;rft.date=24+December+1999&amp;rft.volume=286&amp;rft.issue=5449&amp;rft.pages=2524%26ndash%3B2525&amp;rft_id=info:doi/10.1126%2Fscience.286.5449.2524&amp;rft_id=info:pmid/10617471&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-65"><strong>^</strong> <cite class="Journal" id="CITEREFCastro_JA.2C_Picornell_A.2C_Ramon_M1998" style="FONT-STYLE: normal">Castro JA, Picornell A, Ramon M (1998). &quot;Mitochondrial DNA: a tool for populational genetics studies&quot;. <em>Int Microbiol.</em> <strong>1</strong> (4): 327&ndash;32. PMID 10943382.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondrial+DNA%3A+a+tool+for+populational+genetics+studies&amp;rft.jtitle=Int+Microbiol.&amp;rft.aulast=Castro+JA%2C+Picornell+A%2C+Ramon+M&amp;rft.au=Castro+JA%2C+Picornell+A%2C+Ramon+M&amp;rft.date=1998&amp;rft.volume=1&amp;rft.issue=4&amp;rft.pages=327%E2%80%9332&amp;rft_id=info:pmid/10943382&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-66"><strong>^</strong> <cite class="Journal" id="CITEREFCann_RL.2C_Stoneking_M.2C_Wilson_AC1987" style="FONT-STYLE: normal">Cann RL, Stoneking M, Wilson AC (1987 January). &quot;Mitochondrial DNA and human evolution&quot;. <em>Nature.</em> <strong>325</strong>: 31&ndash;36. doi:<span class="neverexpand">10.1038/325031a0</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondrial+DNA+and+human+evolution&amp;rft.jtitle=Nature.&amp;rft.aulast=Cann+RL%2C+Stoneking+M%2C+Wilson+AC&amp;rft.au=Cann+RL%2C+Stoneking+M%2C+Wilson+AC&amp;rft.date=1987+January&amp;rft.volume=325&amp;rft.pages=31%E2%80%9336&amp;rft_id=info:doi/10.1038%2F325031a0&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-67"><strong>^</strong> <cite class="Journal" id="CITEREFTorroni_A.2C_Achilli_A.2C_Macaulay_V.2C_Richards_M.2C_Bandelt_HJ2006" style="FONT-STYLE: normal">Torroni A, Achilli A, Macaulay V, Richards M, Bandelt HJ (2006). &quot;Harvesting the fruit of the human mtDNA tree&quot;. <em>Trends Genet.</em> <strong>22</strong> (6): 339&ndash;45. doi:<span class="neverexpand">10.1016/j.tig.2006.04.001</span>. PMID 16678300.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Harvesting+the+fruit+of+the+human+mtDNA+tree&amp;rft.jtitle=Trends+Genet.&amp;rft.aulast=Torroni+A%2C+Achilli+A%2C+Macaulay+V%2C+Richards+M%2C+Bandelt+HJ&amp;rft.au=Torroni+A%2C+Achilli+A%2C+Macaulay+V%2C+Richards+M%2C+Bandelt+HJ&amp;rft.date=2006&amp;rft.volume=22&amp;rft.issue=6&amp;rft.pages=339%26ndash%3B45&amp;rft_id=info:doi/10.1016%2Fj.tig.2006.04.001&amp;rft_id=info:pmid/16678300&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Garrigan06-68">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <cite class="Journal" id="CITEREFGarrigan_D.2C_Hammer_MF2006" style="FONT-STYLE: normal">Garrigan D, Hammer MF (2006). &quot;Reconstructing human origins in the genomic era&quot;. <em>Nat. Rev. Genet.</em> <strong>7</strong> (9): 669&ndash;80. doi:<span class="neverexpand">10.1038/nrg1941</span>. PMID 16921345.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Reconstructing+human+origins+in+the+genomic+era&amp;rft.jtitle=Nat.+Rev.+Genet.&amp;rft.aulast=Garrigan+D%2C+Hammer+MF&amp;rft.au=Garrigan+D%2C+Hammer+MF&amp;rft.date=2006&amp;rft.volume=7&amp;rft.issue=9&amp;rft.pages=669%26ndash%3B80&amp;rft_id=info:doi/10.1038%2Fnrg1941&amp;rft_id=info:pmid/16921345&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-69"><strong>^</strong> <cite class="Journal" id="CITEREFKrings_M.2C_Stone_A.2C_Schmitz_RW.2C_Krainitzki_H.2C_Stoneking_M.2C_P.C3.A4.C3.A4bo_S1997" style="FONT-STYLE: normal">Krings M, Stone A, Schmitz RW, Krainitzki H, Stoneking M, P&auml;&auml;bo S (1997). &quot;Neandertal DNA sequences and the origin of modern humans&quot;. <em>Cell</em> <strong>90</strong> (1): 19&ndash;30. doi:<span class="neverexpand">10.1016/S0092-8674(00)80310-4</span>. PMID 9230299.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Neandertal+DNA+sequences+and+the+origin+of+modern+humans&amp;rft.jtitle=Cell&amp;rft.aulast=Krings+M%2C+Stone+A%2C+Schmitz+RW%2C+Krainitzki+H%2C+Stoneking+M%2C+P%C3%A4%C3%A4bo+S&amp;rft.au=Krings+M%2C+Stone+A%2C+Schmitz+RW%2C+Krainitzki+H%2C+Stoneking+M%2C+P%C3%A4%C3%A4bo+S&amp;rft.date=1997&amp;rft.volume=90&amp;rft.issue=1&amp;rft.pages=19%26ndash%3B30&amp;rft_id=info:doi/10.1016%2FS0092-8674%2800%2980310-4&amp;rft_id=info:pmid/9230299&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-70"><strong>^</strong> <cite class="Journal" id="CITEREFHarding_RM.2C_Fullerton_SM.2C_Griffiths_RC.2C_Bond_J.2C_Cox_MJ.2C_Schneider_JA.2C_Moulin_DS.2C_Clegg_JB1997" style="FONT-STYLE: normal">Harding RM, Fullerton SM, Griffiths RC, Bond J, Cox MJ, Schneider JA, Moulin DS, Clegg JB (1997 April). &quot;Archaic African and Asian lineages in the genetic ancestry of modern humans&quot;. <em>Am J Hum Genet.</em> <strong>60</strong> (4): 772&ndash;89. PMID 9106523.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Archaic+African+and+Asian+lineages+in+the+genetic+ancestry+of+modern+humans&amp;rft.jtitle=Am+J+Hum+Genet.&amp;rft.aulast=Harding+RM%2C+Fullerton+SM%2C+Griffiths+RC%2C+Bond+J%2C+Cox+MJ%2C+Schneider+JA%2C+Moulin+DS%2C+Clegg+JB&amp;rft.au=Harding+RM%2C+Fullerton+SM%2C+Griffiths+RC%2C+Bond+J%2C+Cox+MJ%2C+Schneider+JA%2C+Moulin+DS%2C+Clegg+JB&amp;rft.date=1997+April&amp;rft.volume=60&amp;rft.issue=4&amp;rft.pages=772%E2%80%9389&amp;rft_id=info:pmid/9106523&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Zeviani-71">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <sup><em><strong>c</strong></em></sup> <cite class="Journal" id="CITEREFZeviani_M.2C_Di_Donato_S2004" style="FONT-STYLE: normal">Zeviani M, Di Donato S (2004). &quot;Mitochondrial disorders&quot;. <em>Brain.</em> <strong>127</strong>: 2153&ndash;2172. doi:<span class="neverexpand">10.1093/brain/awh259</span>. PMID 15358637.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondrial+disorders&amp;rft.jtitle=Brain.&amp;rft.aulast=Zeviani+M%2C+Di+Donato+S&amp;rft.au=Zeviani+M%2C+Di+Donato+S&amp;rft.date=2004&amp;rft.volume=127&amp;rft.pages=2153%26ndash%3B2172&amp;rft_id=info:doi/10.1093%2Fbrain%2Fawh259&amp;rft_id=info:pmid/15358637&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-pmid15861210-72"><strong>^</strong> <cite class="Journal" id="CITEREFTaylor_RW.2C_Turnbull_DM2005" style="FONT-STYLE: normal">Taylor RW, Turnbull DM (2005). &quot;Mitochondrial DNA mutations in human disease&quot;. <em>Nat. Rev. Genet.</em> <strong>6</strong> (5): 389&ndash;402. doi:<span class="neverexpand">10.1038/nrg1606</span>. PMID 15861210.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondrial+DNA+mutations+in+human+disease&amp;rft.jtitle=Nat.+Rev.+Genet.&amp;rft.aulast=Taylor+RW%2C+Turnbull+DM&amp;rft.au=Taylor+RW%2C+Turnbull+DM&amp;rft.date=2005&amp;rft.volume=6&amp;rft.issue=5&amp;rft.pages=389%26ndash%3B402&amp;rft_id=info:doi/10.1038%2Fnrg1606&amp;rft_id=info:pmid/15861210&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-73"><strong>^</strong> <cite class="Journal" id="CITEREFChinnery_PF.2C_Schon_EA2003" style="FONT-STYLE: normal">Chinnery PF, Schon EA (2003). &quot;Mitochondria&quot;. <em>J. Neurol. Neurosurg. Psychiatr.</em> <strong>74</strong> (9): 1188&ndash;99. doi:<span class="neverexpand">10.1136/jnnp.74.9.1188</span>. PMID 12933917.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondria&amp;rft.jtitle=J.+Neurol.+Neurosurg.+Psychiatr.&amp;rft.aulast=Chinnery+PF%2C+Schon+EA&amp;rft.au=Chinnery+PF%2C+Schon+EA&amp;rft.date=2003&amp;rft.volume=74&amp;rft.issue=9&amp;rft.pages=1188%26ndash%3B99&amp;rft_id=info:doi/10.1136%2Fjnnp.74.9.1188&amp;rft_id=info:pmid/12933917&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-74"><strong>^</strong> <cite class="Journal" id="CITEREFSherer_TB.2C_Betarbet_R.2C_Greenamyre_JT2002" style="FONT-STYLE: normal">Sherer TB, Betarbet R, Greenamyre JT (2002). &quot;Environment, mitochondria, and Parkinson's disease&quot;. <em>The Neuroscientist.</em> <strong>8</strong> (3): 192&ndash;7. doi:<span class="neverexpand">10.1177/1073858402008003004</span>. PMID 12061498.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Environment%2C+mitochondria%2C+and+Parkinson%27s+disease&amp;rft.jtitle=The+Neuroscientist.&amp;rft.aulast=Sherer+TB%2C+Betarbet+R%2C+Greenamyre+JT&amp;rft.au=Sherer+TB%2C+Betarbet+R%2C+Greenamyre+JT&amp;rft.date=2002&amp;rft.volume=8&amp;rft.issue=3&amp;rft.pages=192%26ndash%3B7&amp;rft_id=info:doi/10.1177%2F1073858402008003004&amp;rft_id=info:pmid/12061498&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-75"><strong>^</strong> <cite class="Journal" id="CITEREFGomez_C.2C_Bandez_MJ.2C_Navarro_A2007" style="FONT-STYLE: normal">Gomez C, Bandez MJ, Navarro A (2007). &quot;Pesticides and impairment of mitochondrial function in relation with the parkinsonian syndrome&quot;. <em>Front. Biosci.</em> <strong>12</strong>: 1079&ndash;93. doi:<span class="neverexpand">10.2741/2128</span>. PMID 17127363.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Pesticides+and+impairment+of+mitochondrial+function+in+relation+with+the+parkinsonian+syndrome&amp;rft.jtitle=Front.+Biosci.&amp;rft.aulast=Gomez+C%2C+Bandez+MJ%2C+Navarro+A&amp;rft.au=Gomez+C%2C+Bandez+MJ%2C+Navarro+A&amp;rft.date=2007&amp;rft.volume=12&amp;rft.pages=1079%26ndash%3B93&amp;rft_id=info:doi/10.2741%2F2128&amp;rft_id=info:pmid/17127363&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-76"><strong>^</strong> <cite class="Journal" id="CITEREFSchapira_AH2006" style="FONT-STYLE: normal">Schapira AH (2006). &quot;Mitochondrial disease&quot;. <em>Lancet</em> <strong>368</strong> (9529): 70&ndash;82. doi:<span class="neverexpand">10.1016/S0140-6736(06)68970-8</span>. PMID 16815381.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondrial+disease&amp;rft.jtitle=Lancet&amp;rft.aulast=Schapira+AH&amp;rft.au=Schapira+AH&amp;rft.date=2006&amp;rft.volume=368&amp;rft.issue=9529&amp;rft.pages=70%26ndash%3B82&amp;rft_id=info:doi/10.1016%2FS0140-6736%2806%2968970-8&amp;rft_id=info:pmid/16815381&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-Pieczenik-77">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <cite class="Journal" id="CITEREFPieczenik_SR.2C_Neustadt_J2007" style="FONT-STYLE: normal">Pieczenik SR, Neustadt J (2007). &quot;Mitochondrial dysfunction and molecular pathways of disease&quot;. <em>Exp. Mol. Pathol.</em> <strong>83</strong> (1): 84&ndash;92. doi:<span class="neverexpand">10.1016/j.yexmp.2006.09.008</span>. PMID 17239370.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Mitochondrial+dysfunction+and+molecular+pathways+of+disease&amp;rft.jtitle=Exp.+Mol.+Pathol.&amp;rft.aulast=Pieczenik+SR%2C+Neustadt+J&amp;rft.au=Pieczenik+SR%2C+Neustadt+J&amp;rft.date=2007&amp;rft.volume=83&amp;rft.issue=1&amp;rft.pages=84%26ndash%3B92&amp;rft_id=info:doi/10.1016%2Fj.yexmp.2006.09.008&amp;rft_id=info:pmid/17239370&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-78"><strong>^</strong> <cite class="Journal" id="CITEREFRichter_C.2C_Park_J.2C_Ames_BN1988" style="FONT-STYLE: normal">Richter C, Park J, Ames BN (1988 September). &quot;Normal Oxidative Damage to Mitochondrial and Nuclear DNA is Extensive&quot;. <em>PNAS</em> <strong>85</strong> (17): 6465&ndash;6467. doi:<span class="neverexpand">10.1073/pnas.85.17.6465</span>. PMID 3413108.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Normal+Oxidative+Damage+to+Mitochondrial+and+Nuclear+DNA+is+Extensive&amp;rft.jtitle=PNAS&amp;rft.aulast=Richter+C%2C+Park+J%2C+Ames+BN&amp;rft.au=Richter+C%2C+Park+J%2C+Ames+BN&amp;rft.date=1988+September&amp;rft.volume=85&amp;rft.issue=17&amp;rft.pages=6465%26ndash%3B6467&amp;rft_id=info:doi/10.1073%2Fpnas.85.17.6465&amp;rft_id=info:pmid/3413108&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-79"><strong>^</strong> &quot;Mitochondria and Aging.&quot;. </li>
+    <li id="cite_note-80"><strong>^</strong> <cite class="Journal" id="CITEREFBoffoli_D.2C_Scacco_SC.2C_Vergari_R.2C_Solarino_G.2C_Santacroce_G.2C_Papa_S1994" style="FONT-STYLE: normal">Boffoli D, Scacco SC, Vergari R, Solarino G, Santacroce G, Papa S (1994). &quot;Decline with age of the respiratory chain activity in human skeletal muscle&quot;. <em>Biochim. Biophys. Acta.</em> <strong>1226</strong>: 73&ndash;82. PMID 8155742.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Decline+with+age+of+the+respiratory+chain+activity+in+human+skeletal+muscle&amp;rft.jtitle=Biochim.+Biophys.+Acta.&amp;rft.aulast=Boffoli+D%2C+Scacco+SC%2C+Vergari+R%2C+Solarino+G%2C+Santacroce+G%2C+Papa+S&amp;rft.au=Boffoli+D%2C+Scacco+SC%2C+Vergari+R%2C+Solarino+G%2C+Santacroce+G%2C+Papa+S&amp;rft.date=1994&amp;rft.volume=1226&amp;rft.pages=73%26ndash%3B82&amp;rft_id=info:pmid/8155742&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-81"><strong>^</strong> <cite class="Journal" id="CITEREFBender_A.2C_Krishnan_KJ.2C_Morris_CM.2C_Taylor_GA.2C_Reeve_AK.2C_Perry_RH.2C_Jaros_E.2C_Hersheson_JS.2C_Betts_J.2C_Klopstock_T.2C_Taylor_RW.2C_Turnbull_DM2006" style="FONT-STYLE: normal">Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, Taylor RW, Turnbull DM (2006). &quot;High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease&quot;. <em>Nat Gen.</em> <strong>38</strong>: 515&ndash;517. doi:<span class="neverexpand">10.1038/ng1769</span>. PMID 16604074.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=High+levels+of+mitochondrial+DNA+deletions+in+substantia+nigra+neurons+in+aging+and+Parkinson+disease&amp;rft.jtitle=Nat+Gen.&amp;rft.aulast=Bender+A%2C+Krishnan+KJ%2C+Morris+CM%2C+Taylor+GA%2C+Reeve+AK%2C+Perry+RH%2C+Jaros+E%2C+Hersheson+JS%2C+Betts+J%2C+Klopstock+T%2C+Taylor+RW%2C+Turnbull+DM&amp;rft.au=Bender+A%2C+Krishnan+KJ%2C+Morris+CM%2C+Taylor+GA%2C+Reeve+AK%2C+Perry+RH%2C+Jaros+E%2C+Hersheson+JS%2C+Betts+J%2C+Klopstock+T%2C+Taylor+RW%2C+Turnbull+DM&amp;rft.date=2006&amp;rft.volume=38&amp;rft.pages=515%26ndash%3B517&amp;rft_id=info:doi/10.1038%2Fng1769&amp;rft_id=info:pmid/16604074&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-82"><strong>^</strong> <cite class="Journal" id="CITEREFHarman_D1956" style="FONT-STYLE: normal">Harman D (1956). &quot;Aging: a theory based on free radical and radiation chemistry&quot;. <em>J. Gerontol.</em> <strong>11</strong>: 298&ndash;300. PMID 13332224.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Aging%3A+a+theory+based+on+free+radical+and+radiation+chemistry&amp;rft.jtitle=J.+Gerontol.&amp;rft.aulast=Harman+D&amp;rft.au=Harman+D&amp;rft.date=1956&amp;rft.volume=11&amp;rft.pages=298%26ndash%3B300&amp;rft_id=info:pmid/13332224&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+    <li id="cite_note-83"><strong>^</strong> <cite class="Journal" id="CITEREFTrifunovic_A.2C_Hansson_A.2C_Wredenberg_A.2C_Rovio_AT.2C_Dufour_E.2C_Khvorostov_I.2C_Spelbrink_JN.2C_Wibom_R.2C_Jacobs_HT.2C_Larsson_NG2005" style="FONT-STYLE: normal">Trifunovic A, Hansson A, Wredenberg A, Rovio AT, Dufour E, Khvorostov I, Spelbrink JN, Wibom R, Jacobs HT, Larsson NG (2005). &quot;Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production&quot;. <em>PNAS.</em> <strong>102</strong> (50): 17993&ndash;8. doi:<span class="neverexpand">10.1073/pnas.0508886102</span>. PMID 16332961.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Somatic+mtDNA+mutations+cause+aging+phenotypes+without+affecting+reactive+oxygen+species+production&amp;rft.jtitle=PNAS.&amp;rft.aulast=Trifunovic+A%2C+Hansson+A%2C+Wredenberg+A%2C+Rovio+AT%2C+Dufour+E%2C+Khvorostov+I%2C+Spelbrink+JN%2C+Wibom+R%2C+Jacobs+HT%2C+Larsson+NG&amp;rft.au=Trifunovic+A%2C+Hansson+A%2C+Wredenberg+A%2C+Rovio+AT%2C+Dufour+E%2C+Khvorostov+I%2C+Spelbrink+JN%2C+Wibom+R%2C+Jacobs+HT%2C+Larsson+NG&amp;rft.date=2005&amp;rft.volume=102&amp;rft.issue=50&amp;rft.pages=17993%26ndash%3B8&amp;rft_id=info:doi/10.1073%2Fpnas.0508886102&amp;rft_id=info:pmid/16332961&amp;rfr_id=info:sid/en.wikipedia.org:Mitochondrion"><span style="DISPLAY: none">&nbsp;</span></span> </li>
+</ol>
+</div>
+<p><a name="[문서의 처음]"></a></p>
+<h2><span class="mw-headline">See also</span></h2>
+<div class="infobox sisterproject">
+<div style="FLOAT: left" align="left">&nbsp;</div>
+<div style="MARGIN-LEFT: 60px">Wikimedia Commons has media related to:
+<div style="MARGIN-LEFT: 10px"><em><strong>Mitochondrion</strong></em></div>
+</div>
+</div>
+<ul>
+    <li>Anti-mitochondrial antibodies </li>
+    <li>Bioenergetics </li>
+    <li>Human mitochondrial genetics </li>
+    <li>Mitochondrial permeability transition pore </li>
+    <li>Submitochondrial particle </li>
+</ul>
+<p><a name="#4910c37d"></a></p>
+<h2><span class="mw-headline">External links</span></h2>
+<ul>
+    <li><a class="external text" title="http://www.uni-mainz.de/FB/Medizin/Anatomie/workshop/EM/EMMitoE.html" rel="nofollow" href="http://www.uni-mainz.de/FB/Medizin/Anatomie/workshop/EM/EMMitoE.html">Mitochondria Atlas</a> at <a title="University of Mainz" href="http://en.wikipedia.org/wiki/University_of_Mainz">University of Mainz</a> </li>
+    <li><a class="external text" title="http://www.mitochondrial.net" rel="nofollow" href="http://www.mitochondrial.net/">Mitochondria Research Portal</a> at mitochondrial.net </li>
+    <li><a class="external text" title="http://www.cytochemistry.net/Cell-biology/mitoch1.htm" rel="nofollow" href="http://www.cytochemistry.net/Cell-biology/mitoch1.htm">Mitochondria: Architecture dictates function</a> at cytochemistry.net </li>
+    <li><a class="external text" title="http://bama.ua.edu/~hsmithso/class/bsc_495/mito-plastids/mito_web.html" rel="nofollow" href="http://bama.ua.edu/~hsmithso/class/bsc_495/mito-plastids/mito_web.html">Mitochondria links</a> at <a title="University of Alabama" href="http://en.wikipedia.org/wiki/University_of_Alabama">University of Alabama</a> </li>
+    <li><a class="external text" title="http://www.mitophysiology.org/" rel="nofollow" href="http://www.mitophysiology.org/">MIP</a> Mitochondrial Physiology Society </li>
+    <li><a class="external text" title="http://www.sci.sdsu.edu/TFrey/MitoMovie.htm" rel="nofollow" href="http://www.sci.sdsu.edu/TFrey/MitoMovie.htm">Mitochondrion Reconstructed by Electron Tomography</a> at <a title="San Diego State University" href="http://en.wikipedia.org/wiki/San_Diego_State_University">San Diego State University</a> </li>
+    <li><a class="external text" title="http://www.wadsworth.org/databank/electron/cryomito_dis2.html" rel="nofollow" href="http://www.wadsworth.org/databank/electron/cryomito_dis2.html">Video Clip of Rat-liver Mitochondrion from Cryo-electron Tomography</a> at wadsworth.org </li>
+    <li><a class="external text" title="http://opm.phar.umich.edu/localization.php?localization=Mitochondrial%20inner%20membrane" rel="nofollow" href="http://opm.phar.umich.edu/localization.php?localization=Mitochondrial%20inner%20membrane">3D structures of proteins from inner mitochondrial membrane</a> at <a title="University of Michigan" href="http://en.wikipedia.org/wiki/University_of_Michigan">University of Michigan</a> </li>
+    <li><a class="external text" title="http://opm.phar.umich.edu/localization.php?localization=Mitochondrial%20outer%20membrane" rel="nofollow" href="http://opm.phar.umich.edu/localization.php?localization=Mitochondrial%20outer%20membrane">3D structures of proteins associated with outer mitochondrial membrane</a> at <a title="University of Michigan" href="http://en.wikipedia.org/wiki/University_of_Michigan">University of Michigan</a> </li>
+</ul>
+<p>&nbsp;</p>

Difference between revisions of "Mitochondria"

Latest revision as of 21:26, 30 November 2008

Contents

Structure

Outer membrane

Intermembrane space

Inner membrane

Cristae

Matrix

Organization and distribution

Function

Energy conversion

Pyruvate: the citric acid cycle

NADH and FADH2: the electron transport chain 미토콘드리아

Heat production

Storage of calcium ions

Additional functions

Origin

Genome

Replication and inheritance

Population genetic studies

Dysfunction and disease

Mitochondrial diseases

Possible relationships to aging

References

See also

External links

Navigation menu

Search

Related Links[Edit]

NADH and FADH₂: the electron transport chain

미토콘드리아