View source for MT-ATP8

{{Short description|A mitochondrial protein-coding gene whose product is involved in ATP synthesis}}
{{Infobox_gene}}
[[File:Map of the human mitochondrial genome.svg|thumb|320px|Location of the ''MT-ATP8'' gene in the human mitochondrial genome. ''MT-ATP8'' is one of the two ATP synthase mitochondrial genes (red boxes).]]
[[File:Homo sapiens-mtDNA~NC 012920-ATP8+ATP6 Overlap.svg|upleft|thumb|left|400px|The 46-nucleotide overlap in the reading frames of the human mitochondrial genes ''MT-ATP8'' and ''MT-ATP6''. For each nucleotide triplet (square brackets), the corresponding amino acid is given (one-letter code), either in the +1 frame for ''MT-ATP8'' (in red) or in the +3 frame for ''MT-ATP6'' (in blue).]]
{{Infobox protein family
| Symbol = ATP-synt_8
| Name = ATP synthase protein 8 (metazoa)
| image = 
| width = 
| caption = 
| Pfam = PF00895
| Pfam_clan = CL0255 
| InterPro = IPR001421
| SMART = 
| PROSITE = 
| MEROPS = 
| SCOP = 
| TCDB = 
| OPM family = 
| OPM protein = 
| CAZy = 
| CDD = 
}}
{{Infobox protein family
| Symbol = YMF19
| Name = Plant ATP synthase F0 subunit 8
| image = 
| width = 
| caption = 
| Pfam = PF02326
| Pfam_clan = CL0255 
| InterPro = IPR003319
| SMART = 
| PROSITE = 
| MEROPS = 
| SCOP = 
| TCDB = 
| OPM family = 
| OPM protein = 
| CAZy = 
| CDD = 
}}
{{Infobox protein family
| Symbol = Fun_ATP-synt_8
| Name = Fungal ATP synthase protein 8 (A6L)
| image = 
| width = 
| caption = 
| Pfam = PF05933
| Pfam_clan = CL0255 
| InterPro = IPR009230
| SMART = 
| PROSITE = 
| MEROPS = 
| SCOP = 
| TCDB = 
| OPM family = 
| OPM protein = 
| CAZy = 
| CDD = 
}}

'''''MT-ATP8''''' (or '''''ATP8''''') is a [[mitochondrial gene]] with the full name 'mitochondrially encoded ATP synthase membrane subunit 8' that encodes a subunit of [[mitochondrial ATPase|mitochondrial ATP synthase]], '''ATP synthase F<sub>o</sub> subunit 8''' (or '''subunit A6L'''). This subunit belongs to the F<sub>o</sub> complex of the large, transmembrane F-type [[ATP synthase]].<ref name="pmid7219534">{{cite journal | vauthors = Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG | title = Sequence and organization of the human mitochondrial genome | journal = Nature | volume = 290 | issue = 5806 | pages = 457–65 | date = April 1981 | pmid = 7219534 | doi = 10.1038/290457a0 }}</ref> This enzyme, which is also known as complex V, is responsible for the final step of [[oxidative phosphorylation]] in the [[electron transport chain]]. Specifically, one segment of ATP synthase allows positively charged [[ions]], called [[protons]], to flow across a specialized membrane inside mitochondria. Another segment of the enzyme uses the energy created by this proton flow to convert a molecule called [[adenosine diphosphate]] (ADP) to [[adenosine triphosphate | ATP]].<ref name = "GHR">{{ cite web| url = http://ghr.nlm.nih.gov/gene/MT-ATP8 | work = Genetics Home Reference | title = MT-ATP8 | publisher = NCBI}}</ref> Subunit 8 differs in [[sequence (biology)|sequence]] between [[Metazoa]], [[plants]] and [[fungus|Fungi]].

== Structure ==
The ATP synthase protein 8 of human and other mammals is encoded in the [[mitochondrial genome]] by the ''MT-ATP8'' [[gene]]. When the complete human mitochondrial genome was first published, the ''MT-ATP8'' gene was described as the unidentified [[Reading frame#Open reading frame|reading frame]] ''[[Unidentified reading frame|URF]] A6L''.<ref name="pmid7219534"/> An unusual feature of the ''MT-ATP8'' gene is its 46-nucleotide overlap with the ''[[MT-ATP6]]'' gene. With respect to the reading frame (+1) of ''MT-ATP8'', the ''MT-ATP6'' gene starts on the +3 reading frame.

The MT-ATP8 protein weighs 8 kDa and is composed of 68 [[amino acids]].<ref name=COPaKB>{{vcite2 journal | vauthors = Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = Oct 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}</ref><ref name="url_COPaKB">{{cite web | url = https://amino.heartproteome.org/web/protein/P03928 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = ATP synthase protein 8 }}</ref> The protein is a subunit of the F<sub>1</sub>F<sub>o</sub> ATPase, also known as [[Complex V]], which consists of 14 nuclear- and 2 mitochondrial-encoded subunits. F-type ATPases consist of two structural domains, F<sub>1</sub> containing the extramembraneous catalytic core and F<sub>o</sub> containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. As an A subunit, MT-ATP8 is contained within the non-catalytic, [[transmembrane]] F<sub>o</sub> portion of the complex, comprising the [[proton channel]]. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the delta subunit of the catalytic core. Alternatively spliced transcript variants encoding the same isoform have been identified.<ref name="entrez">{{cite web |title=MT-ATP8 mitochondrially encoded ATP synthase 8 [Homo sapiens (human)] |url=https://www.ncbi.nlm.nih.gov/gene/4509|work = Gene |publisher=NCBI}}</ref><ref name="GHR" />

== Function ==
The MT-ATP8 ''gene'' encodes a subunit of mitochondrial [[ATP synthase]], located within the [[thylakoid membrane]] and the [[inner mitochondrial membrane]]. Mitochondrial ATP synthase [[catalyzes]] ATP synthesis, utilizing an [[electrochemical gradient]] of [[protons]] across the inner membrane during [[oxidative phosphorylation]].<ref name="entrez" /> The F<sub>o</sub> region causes rotation of F<sub>1</sub>, which has a water-soluble component that hydrolyzes ATP and together, the F<sub>1</sub>F<sub>o</sub> creates a pathway for movement of protons across the membrane.<ref name="Velours_2000">{{cite journal | vauthors = Velours J, Paumard P, Soubannier V, Spannagel C, Vaillier J, Arselin G, Graves PV | title = Organisation of the yeast ATP synthase F(0):a study based on cysteine mutants, thiol modification and cross-linking reagents | journal = Biochimica et Biophysica Acta | volume = 1458 | issue = 2-3 | pages = 443–56 | date = May 2000 | pmid = 10838057 | doi = 10.1016/S0005-2728(00)00093-1 }}</ref>

This [[protein]] subunit appears to be an integral component of the stator stalk in [[Saccharomyces cerevisiae|yeast]] [[mitochondrial]] [[F-ATPase]]s.<ref name="pmid12626501">{{cite journal | vauthors = Stephens AN, Khan MA, Roucou X, Nagley P, Devenish RJ | title = The molecular neighborhood of subunit 8 of yeast mitochondrial F1F0-ATP synthase probed by cysteine scanning mutagenesis and chemical modification | journal = The Journal of Biological Chemistry | volume = 278 | issue = 20 | pages = 17867–75 | date = May 2003 | pmid = 12626501 | doi = 10.1074/jbc.M300967200 }}</ref> The stator stalk is anchored in the [[membrane]], and acts to prevent futile rotation of the ATPase subunits relative to the rotor during coupled ATP synthesis/hydrolysis. This subunit may have an analogous function in [[Metazoa]].

== Nomenclature ==
The [[nomenclature]] of the enzyme has a long history. The F<sub>1</sub> fraction derives its name from the term "Fraction 1" and F<sub>o</sub> (written as a subscript letter "o", not "zero") derives its name from being the binding fraction for [[oligomycin]], a type of naturally-derived antibiotic that is able to inhibit the F<sub>o</sub> unit of ATP synthase.<ref name="cite pmid| 4223640">{{cite journal | vauthors = Kagawa Y, Racker E | title = Partial resolution of the enzymes catalyzing oxidative phosphorylation. 8. Properties of a factor conferring oligomycin sensitivity on mitochondrial adenosine triphosphatase | journal = The Journal of Biological Chemistry | volume = 241 | issue = 10 | pages = 2461–6 | date = May 1966 | pmid = 4223640 }}</ref><ref>{{cite journal | vauthors = Mccarty RE | title = A PLANT BIOCHEMIST'S VIEW OF H+-ATPases AND ATP SYNTHASES | journal = The Journal of Experimental Biology | volume = 172 | issue = Pt 1 | pages = 431–441 | date = November 1992 | pmid = 9874753 | doi =  | url = http://jeb.biologists.org/cgi/reprint/172/1/431 }}</ref> The F<sub>o</sub> region of ATP synthase is a proton pore that is embedded in the mitochondrial membrane. It consists of three main subunits A, B, and C, and (in humans) six additional subunits, [[ATP5H|d]], [[ATP5I|e]], [[ATP5J2|f]], [[ATP5L|g]], [[MT-ATP6]] (or F6), and MT-ATP8 (or A6L). 3D structure of [[Escherichia coli|E. coli]] homologue of this subunit was modeled based on [[electron microscopy]] data (chain M of {{PDB|1c17}}). It forms a transmembrane 4-α-bundle.

==Clinical Significance==
Mutations to MT-ATP8 and other genes affecting [[oxidative phosphorylation]] in the mitochondria have been associated with a variety of [[neurodegenerative]] and [[cardiovascular]] disorders, including mitochondrial complex V deficiency, [[Leber's hereditary optic neuropathy]] (LHON), mitochondrial encephalomyopathy with stroke-like episodes ([[MELAS]]), [[Leigh syndrome]], and [[Neuropathy, ataxia, and retinitis pigmentosa |NARP syndrome]]. Most of the body's cells contain thousands of mitochondria, each with one or more copies of [[mitochondrial DNA]]. The severity of some [[mitochondrial disease|mitochondrial disorders]] is associated with the percentage of mitochondria in each cell that has a particular genetic change. People with [[Leigh syndrome]] due to a MT-ATP6 gene mutation tend to have a very high percentage of mitochondria with the mutation (from more than 90 percent to 95 percent). The less-severe features of [[Neuropathy, ataxia, and retinitis pigmentosa |NARP]] result from a lower percentage of mitochondria with the mutation, typically 70 percent to 90 percent. Because these two conditions result from the same genetic changes and can occur in different members of a single family, researchers believe that they may represent a spectrum of overlapping features instead of two distinct syndromes.<ref name = GHR />

Mitochondrial complex V deficiency presents with heterogeneous clinical manifestations including [[neuropathy]], [[ataxia]], [[hypertrophic cardiomyopathy]]. Hypertrophic cardiomyopathy can present with negligible to extreme [[hypertrophy]], minimal to extensive [[fibrosis]] and [[myocyte]] disarray, absent to severe left ventricular outflow tract obstruction, and distinct septal contours/morphologies with extremely varying clinical course.<ref name = "UniProt">{{cite web |title=MT-ATP8 - ATP synthase protein 8 - Homo sapiens (Human) |url=https://www.uniprot.org/uniprot/P03928 |website=www.uniprot.org |publisher=UniProt |access-date=3 August 2018 |language=en}} {{CC-notice|cc=by4}}</ref><ref name = "Ware">{{cite journal | vauthors = Ware SM, El-Hassan N, Kahler SG, Zhang Q, Ma YW, Miller E, Wong B, Spicer RL, Craigen WJ, Kozel BA, Grange DK, Wong LJ | title = Infantile cardiomyopathy caused by a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes | journal = Journal of Medical Genetics | volume = 46 | issue = 5 | pages = 308–14 | date = May 2009 | pmid = 19188198 | doi = 10.1136/jmg.2008.063149 }}</ref>

Mitochondrial complex V deficiency is a shortage (deficiency) or loss of function in [[complex V]] of the [[electron transport chain]] that can cause a wide variety of [[medical sign|signs and symptoms]] affecting many organs and systems of the body, particularly the [[nervous system]] and the [[heart]]. The disorder can be life-threatening in infancy or early childhood. Affected individuals may have feeding problems, slow growth, low muscle tone ([[hypotonia]]), extreme fatigue ([[lethargy]]), and [[developmental delay]]. They tend to develop elevated levels of [[lactic acid]] in the blood ([[lactic acidosis]]), which can cause nausea, vomiting, weakness, and rapid breathing. High levels of [[ammonia]] in the blood ([[hyperammonemia]]) can also occur in affected individuals, and in some cases result in abnormal brain function ([[encephalopathy]]) and damage to other organs.<ref name="GHRcV">{{cite web |title=Mitochondrial complex V deficiency |url=https://ghr.nlm.nih.gov/condition/mitochondrial-complex-v-deficiency |work = Genetics Home Reference | publisher = NCBI|access-date=3 August 2018 |language=en}} {{PD-notice}}</ref> [[Ataxia]], [[microcephaly]], developmental delay and intellectual disability have been observed in patients with a frameshift mutation in MT-ATP6. This causes a C insertion at position 8612 that results in a truncated protein only 36 amino acids long, and two T > C [[single-nucleotide polymorphisms]] at positions 8610 and 8614 that result in a homopolymeric [[cytosine]] stretch.<ref>{{cite journal | vauthors = Jackson CB, Hahn D, Schröter B, Richter U, Battersby BJ, Schmitt-Mechelke T, Marttinen P, Nuoffer JM, Schaller A | title = A novel mitochondrial ATP6 frameshift mutation causing isolated complex V deficiency, ataxia and encephalomyopathy | journal = European Journal of Medical Genetics | volume = 60 | issue = 6 | pages = 345–351 | date = June 2017 | pmid = 28412374 | doi = 10.1016/j.ejmg.2017.04.006 }}</ref>

[[Hypertrophic cardiomyopathy]], a common feature of mitochondrial complex V deficiency, is characterized by thickening ([[hypertrophy]]) of the [[cardiac muscle]] that can lead to [[heart failure]].<ref name="GHRcV"/> The m.8528T>C mutation occurs in the overlapping region of the MT-ATP6 and MT-ATP8 genes and has been described in multiple patients with infantile cardiomyopathy. This mutation changes the initiation codon in MT-ATP6 to [[threonine]] as well as a change from [[tryptophan]] to [[arginine]] at position 55 of MT-ATP8.<ref>{{cite journal | vauthors = Imai A, Fujita S, Kishita Y, Kohda M, Tokuzawa Y, Hirata T, Mizuno Y, Harashima H, Nakaya A, Sakata Y, Takeda A, Mori M, Murayama K, Ohtake A, Okazaki Y | title = Rapidly progressive infantile cardiomyopathy with mitochondrial respiratory chain complex V deficiency due to loss of ATPase 6 and 8 protein | journal = International Journal of Cardiology | volume = 207 | pages = 203–5 | date = March 2016 | pmid = 26803244 | doi = 10.1016/j.ijcard.2016.01.026 }}</ref><ref name="Ware" /> Individuals with mitochondrial complex V deficiency may also have a characteristic pattern of facial features, including a high forehead, curved eyebrows, outside corners of the eyes that point downward (downslanting [[palpebral fissures]]), a prominent bridge of the nose, low-set ears, thin lips, and a small chin ([[micrognathia]]).<ref name="GHRcV"/>

Infantile hypertrophic cardiomyopathy (CMHI) is also caused by mutations affecting distinct [[genetic loci]], including [[MT-ATP6]] and MT-ATP8. An infantile form of [[hypertrophic cardiomyopathy]], a heart disorder characterized by [[ventricular hypertrophy]], which is usually asymmetric and often involves the [[interventricular septum]]. The symptoms include [[dyspnea]], [[syncope (medicine)|syncope]], collapse, [[palpitations]], and [[chest pain]]. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of [[cardiac failure]] and [[sudden cardiac death]].<ref name = "UniProt" /><ref name = "Ware" />

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Torroni A, Achilli A, Macaulay V, Richards M, Bandelt HJ | title = Harvesting the fruit of the human mtDNA tree | journal = Trends in Genetics | volume = 22 | issue = 6 | pages = 339–45 | date = June 2006 | pmid = 16678300 | doi = 10.1016/j.tig.2006.04.001 }}
* {{cite journal | vauthors = Bodenteich A, Mitchell LG, Polymeropoulos MH, Merril CR | title = Dinucleotide repeat in the human mitochondrial D-loop | journal = Human Molecular Genetics | volume = 1 | issue = 2 | pages = 140 | date = May 1992 | pmid = 1301157 | doi = 10.1093/hmg/1.2.140-a }}
* {{cite journal | vauthors = Lu X, Walker T, MacManus JP, Seligy VL | title = Differentiation of HT-29 human colonic adenocarcinoma cells correlates with increased expression of mitochondrial RNA: effects of trehalose on cell growth and maturation | journal = Cancer Research | volume = 52 | issue = 13 | pages = 3718–25 | date = July 1992 | pmid = 1377597 | doi =  }}
* {{cite journal | vauthors = Marzuki S, Noer AS, Lertrit P, Thyagarajan D, Kapsa R, Utthanaphol P, Byrne E | title = Normal variants of human mitochondrial DNA and translation products: the building of a reference data base | journal = Human Genetics | volume = 88 | issue = 2 | pages = 139–45 | date = December 1991 | pmid = 1757091 | doi = 10.1007/bf00206061 }}
* {{cite journal | vauthors = Moraes CT, Andreetta F, Bonilla E, Shanske S, DiMauro S, Schon EA | title = Replication-competent human mitochondrial DNA lacking the heavy-strand promoter region | journal = Molecular and Cellular Biology | volume = 11 | issue = 3 | pages = 1631–7 | date = March 1991 | pmid = 1996112 | pmc = 369459 | doi =  }}
* {{cite journal | vauthors = Attardi G, Chomyn A, Doolittle RF, Mariottini P, Ragan CI | title = Seven unidentified reading frames of human mitochondrial DNA encode subunits of the respiratory chain NADH dehydrogenase | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 51 Pt 1 | issue = 1 | pages = 103–14 | year = 1987 | pmid = 3472707 | doi = 10.1101/sqb.1986.051.01.013 }}
* {{cite journal | vauthors = Chomyn A, Cleeter MW, Ragan CI, Riley M, Doolittle RF, Attardi G | title = URF6, last unidentified reading frame of human mtDNA, codes for an NADH dehydrogenase subunit | journal = Science | volume = 234 | issue = 4776 | pages = 614–8 | date = October 1986 | pmid = 3764430 | doi = 10.1126/science.3764430 }}
* {{cite journal | vauthors = Chomyn A, Mariottini P, Cleeter MW, Ragan CI, Matsuno-Yagi A, Hatefi Y, Doolittle RF, Attardi G | title = Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory-chain NADH dehydrogenase | journal = Nature | volume = 314 | issue = 6012 | pages = 592–7 | year = 1985 | pmid = 3921850 | doi = 10.1038/314592a0 }}
* {{cite journal | vauthors = Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG | title = Sequence and organization of the human mitochondrial genome | journal = Nature | volume = 290 | issue = 5806 | pages = 457–65 | date = April 1981 | pmid = 7219534 | doi = 10.1038/290457a0 }}
* {{cite journal | vauthors = Montoya J, Ojala D, Attardi G | title = Distinctive features of the 5'-terminal sequences of the human mitochondrial mRNAs | journal = Nature | volume = 290 | issue = 5806 | pages = 465–70 | date = April 1981 | pmid = 7219535 | doi = 10.1038/290465a0 }}
* {{cite journal | vauthors = Horai S, Hayasaka K, Kondo R, Tsugane K, Takahata N | title = Recent African origin of modern humans revealed by complete sequences of hominoid mitochondrial DNAs | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 2 | pages = 532–6 | date = January 1995 | pmid = 7530363 | pmc = 42775 | doi = 10.1073/pnas.92.2.532 }}
* {{cite journal | vauthors = Rieder MJ, Taylor SL, Tobe VO, Nickerson DA | title = Automating the identification of DNA variations using quality-based fluorescence re-sequencing: analysis of the human mitochondrial genome | journal = Nucleic Acids Research | volume = 26 | issue = 4 | pages = 967–73 | date = February 1998 | pmid = 9461455 | pmc = 147367 | doi = 10.1093/nar/26.4.967 }}
* {{cite journal | vauthors = Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N | title = Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA | journal = Nature Genetics | volume = 23 | issue = 2 | pages = 147 | date = October 1999 | pmid = 10508508 | doi = 10.1038/13779 }}
* {{cite journal | vauthors = Ingman M, Kaessmann H, Pääbo S, Gyllensten U | title = Mitochondrial genome variation and the origin of modern humans | journal = Nature | volume = 408 | issue = 6813 | pages = 708–13 | date = December 2000 | pmid = 11130070 | doi = 10.1038/35047064 }}
* {{cite journal | vauthors = Finnilä S, Lehtonen MS, Majamaa K | title = Phylogenetic network for European mtDNA | journal = American Journal of Human Genetics | volume = 68 | issue = 6 | pages = 1475–84 | date = June 2001 | pmid = 11349229 | pmc = 1226134 | doi = 10.1086/320591 }}
* {{cite journal | vauthors = Maca-Meyer N, González AM, Larruga JM, Flores C, Cabrera VM | title = Major genomic mitochondrial lineages delineate early human expansions | journal = BMC Genetics | volume = 2 | pages = 13 | year = 2003 | pmid = 11553319 | pmc = 55343 | doi = 10.1186/1471-2156-2-13 }}
* {{cite journal | vauthors = Herrnstadt C, Elson JL, Fahy E, Preston G, Turnbull DM, Anderson C, Ghosh SS, Olefsky JM, Beal MF, Davis RE, Howell N | title = Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups | journal = American Journal of Human Genetics | volume = 70 | issue = 5 | pages = 1152–71 | date = May 2002 | pmid = 11938495 | pmc = 447592 | doi = 10.1086/339933 }}
* {{cite journal | vauthors = Silva WA, Bonatto SL, Holanda AJ, Ribeiro-Dos-Santos AK, Paixão BM, Goldman GH, Abe-Sandes K, Rodriguez-Delfin L, Barbosa M, Paçó-Larson ML, Petzl-Erler ML, Valente V, Santos SE, Zago MA | title = Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America | journal = American Journal of Human Genetics | volume = 71 | issue = 1 | pages = 187–92 | date = July 2002 | pmid = 12022039 | pmc = 384978 | doi = 10.1086/341358 }}
* {{cite journal | vauthors = Mishmar D, Ruiz-Pesini E, Golik P, Macaulay V, Clark AG, Hosseini S, Brandon M, Easley K, Chen E, Brown MD, Sukernik RI, Olckers A, Wallace DC | title = Natural selection shaped regional mtDNA variation in humans | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 1 | pages = 171–6 | date = January 2003 | pmid = 12509511 | pmc = 140917 | doi = 10.1073/pnas.0136972100 }}
* {{cite journal | vauthors = Ingman M, Gyllensten U | title = Mitochondrial genome variation and evolutionary history of Australian and New Guinean aborigines | journal = Genome Research | volume = 13 | issue = 7 | pages = 1600–6 | date = July 2003 | pmid = 12840039 | pmc = 403733 | doi = 10.1101/gr.686603 }}
{{refend}}


{{Mitochondrial proteins}}
[[Category:Proteins]]
[[Category:Human mitochondrial genes]]

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{{InterPro content|IPR001421}}
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