901:(MRT). Research and clinical applications of MRT were overseen by laws made by federal and state governments. State laws were, for the most part, consistent with federal law. In all states, legislation prohibited the use of MRT techniques in the clinic, and except for Western Australia, research on a limited range of MRT was permissible up to day 14 of embryo development, subject to a license being granted. In 2010, the Hon. Mark Butler MP, then Federal Minister for Mental Health and Ageing, had appointed an independent committee to review the two relevant acts: the
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About 1 in 4,000 children in the United States will develop mitochondrial disease by the age of 10 years. Up to 4,000 children per year in the US are born with a type of mitochondrial disease. Because mitochondrial disorders contain many variations and subsets, some particular mitochondrial disorders
1255:
Abyadeh, Morteza; Gupta, Vivek; Chitranshi, Nitin; Gupta, Veer; Wu, Yunqi; Saks, Danit; WanderWall, Roshana; Fitzhenry, Matthew J; Basavarajappa, Devaraj; You, Yuyi; H Hosseini, Ghasem; A Haynes, Paul; L Graham, Stuart; Mirzaei, Mehdi (2021). "Mitochondrial dysfunction in
Alzheimer's disease - a
1473:
Misiewicz, Zuzanna; Iurato, Stella; Kulesskaya, Natalia; Salminen, Laura; Rodrigues, Luis; Maccarrone, Giuseppina; Martins, Jade; Czamara, Darina; Laine, Mikaela A.; Sokolowska, Ewa; Trontti, Kalevi; Rewerts, Christiane; Novak, Bozidar; Volk, Naama; Park, Dong Ik; Jokitalo, Eija; Paulin, Lars;
586:
Although mitochondrial diseases vary greatly in presentation from person to person, several major clinical categories of these conditions have been defined, based on the most common phenotypic features, symptoms, and signs associated with the particular mutations that tend to cause them.
2221:
Bulduk, Bengisu Kevser; Kiliç, Hasan Basri; Bekircan-Kurt, Can Ebru; Haliloğlu, Göknur; Erdem Özdamar, Sevim; Topaloğlu, Haluk; Kocaefe, Y. Çetin (March 2020). "A Novel
Amplification-Refractory Mutation System-PCR Strategy to Screen MT-TL1 Pathogenic Variants in Patient Repositories".
857:
successfully transplanted healthy DNA in human eggs from women with mitochondrial disease into the eggs of women donors who were unaffected. In such cases, ethical questions have been raised regarding biological motherhood, since the child receives genes and gene regulatory molecules
912:
Currently, human clinical trials are underway at GenSight
Biologics (ClinicalTrials.gov # NCT02064569) and the University of Miami (ClinicalTrials.gov # NCT02161380) to examine the safety and efficacy of mitochondrial gene therapy in Leber's hereditary optic neuropathy.
744:
generation capacity, and is used to compare the mitochondrial output of affected or chronically glycogen-depleted individuals to healthy individuals. This value is slow to change in a given individual, as it takes between 18 and 24 months to complete a full cycle.
556:
The body, and each mutation, is modulated by other genome variants; the mutation that in one individual may cause liver disease might in another person cause a brain disorder. The severity of the specific defect may also be great or small. Some defects include
2007:
Sparks, Lauren M.; Xie, Hui; Koza, Robert A.; Mynatt, Randall; Hulver, Matthew W.; Bray, George A.; Smith, Steven R. (July 2005). "A High-Fat Diet
Coordinately Downregulates Genes Required for Mitochondrial Oxidative Phosphorylation in Skeletal Muscle".
632:
Example of a pedigree for a genetic trait inherited by mitochondrial DNA in animals and humans. Offspring of the males with the trait don't inherit the trait. Offspring of the females with the trait always inherit the trait (independently from their own
656:
the mitochondria segregate randomly between the two new cells. Those mitochondria make more copies, normally reaching 500 mitochondria per cell. As mtDNA is copied when mitochondria proliferate, they can accumulate random mutations, a phenomenon called
3165:
728:) explored the role of mitochondria in insulin resistance among the offspring of patients with type 2 diabetes. Other studies have shown that the mechanism may involve the interruption of the mitochondrial signaling process in body cells (
768:. The energy output of full healthy mitochondrial function can be predicted exactly by a complicated theoretical argument, but this argument is not straightforward, as most energy is consumed by the brain and is not easily measurable.
822:, it is hypothesized that N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), and melatonin could be potential treatment options.
2392:
Nierenberg, Andrew A, Kansky, Christine, Brennan, Brian P, Shelton, Richard C, Perlis, Roy, Iosifescu, Dan V (2012). "Mitochondrial modulators for bipolar disorder: A pathophysiologically informed paradigm for new drug development".
1378:
Nierenberg, Andrew A; Kansky, Christine; Brennan, Brian P; Shelton, Richard C; Perlis, Roy; Iosifescu, Dan V (2012). "Mitochondrial modulators for bipolar disorder: A pathophysiologically informed paradigm for new drug development".
376:
LHON is an eye disorder characterized by progressive loss of central vision due to degeneration of the optic nerves and retina (apparently affecting between 1 in 30,000 and 1 in 50,000 people); visual loss typically begins in young
661:. If only a few of the mtDNA copies inherited from the mother are defective, mitochondrial division may cause most of the defective copies to end up in just one of the new mitochondria (for more detailed inheritance patterns, see
691:, while most of the estimated 1,500 proteins and components targeted to mitochondria are nuclear-encoded. Defects in nuclear-encoded mitochondrial genes are associated with hundreds of clinical disease phenotypes including
2751:
Gorman, Gráinne S.; Grady, John P.; Ng, Yi; Schaefer, Andrew M.; McNally, Richard J.; Chinnery, Patrick F.; Yu-Wai-Man, Patrick; Herbert, Mary; Taylor, Robert W.; McFarland, Robert; Turnbull, Doug M. (26 February 2015).
2516:
Craven, Lyndsey; Tuppen, Helen A.; Greggains, Gareth D.; Harbottle, Stephen J.; Murphy, Julie L.; Cree, Lynsey M.; Murdoch, Alison P.; Chinnery, Patrick F.; Taylor, Robert W.; Lightowlers, Robert N.; Herbert, Mary;
869:
In
September 2012 a public consultation was launched in the UK to explore the ethical issues involved. Human genetic engineering was used on a small scale to allow infertile women with genetic defects in their
215:
Mitochondrial diseases take on unique characteristics both because of the way the diseases are often inherited and because mitochondria are so critical to cell function. A subclass of these diseases that have
882:' procedure as a treatment to fix or eliminate mitochondrial diseases that are passed on from mother to child. The procedure could be offered from 29 October 2015 once regulations had been established.
564:
It has also been reported that drug tolerant cancer cells have an increased number and size of mitochondria, which suggested an increase in mitochondrial biogenesis. Interestingly, a recent study in
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has two copies per cell (except for sperm and egg cells), one copy being inherited from the father and the other from the mother. Mitochondrial DNA, however, is inherited from the mother only (with
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Mitochondrial diseases are usually detected by analysing muscle samples, where the presence of these organelles is higher. The most common tests for the detection of these diseases are:
1772:
Lax, Nichola Zoe; Hepplewhite, Philippa Denis; Reeve, Amy
Katherine; Nesbitt, Victoria; McFarland, Robert; Jaros, Evelyn; Taylor, Robert William; Turnbull, Douglass Matthew (2012).
672:
Mitochondria possess many of the same DNA repair pathways as nuclei do—but not all of them; therefore, mutations occur more frequently in mitochondrial DNA than in nuclear DNA (see
732:). A study conducted at the Pennington Biomedical Research Center in Baton Rouge, Louisiana showed that this, in turn, partially disables the genes that produce mitochondria.
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2603:
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An outstanding question and area of research is whether ATP depletion or reactive oxygen species are in fact responsible for the observed phenotypic consequences.
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The first pathogenic mutation in mitochondrial DNA was identified in 1988; from that time to 2016, around 275 other disease-causing mutations were identified.
3029:
2987:
396:
2801:
Claiborne, A.; English, R.; Kahn, J. (2016). "Etiology, Clinical
Manifestation, and Diagnosis". In Claiborne, Anne; English, Rebecca; Kahn, Jeffrey (eds.).
665:). Mitochondrial disease may become clinically apparent once the number of affected mitochondria reaches a certain level; this phenomenon is called "
2945:
3133:
2982:
370:
255:
53:
862:. Using genetic engineering in attempts to produce babies free of mitochondrial disease is controversial in some circles and raises important
2818:
2622:
1139:
2921:
973:
676:). This means that mitochondrial DNA disorders may occur spontaneously and relatively often. Defects in enzymes that control mitochondrial
466:
2300:
Tanaka M, Nishigaki Y, Fuku N, Ibi T, Sahashi K, Koga Y (2007). "Therapeutic potential of pyruvate therapy for mitochondrial diseases".
334:
Mitochondrial disease can manifest in many different ways whether in children or adults. Examples of mitochondrial diseases include:
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1231:
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830:
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that code for mitochondrial components. They may also be the result of acquired mitochondrial dysfunction due to adverse effects of
321:
302:
119:
100:
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The average number of births per year among women at risk for transmitting mtDNA disease is estimated to approximately 150 in the
274:
72:
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3263:
3253:
3121:
3011:
2953:
2914:
724:
561:. Defects often affect the operation of the mitochondria and multiple tissues more severely, leading to multi-system diseases.
358:
can be found together for other reasons, at an early age this combination can be due to mitochondrial disease, as may occur in
344:
281:
259:
79:
57:
2647:
2084:"A Mitochondria-K+ Channel Axis Is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer Growth"
391:
a rapid decline in function occurs and is marked by seizures, altered states of consciousness, dementia, ventilatory failure
2498:
1474:
Auvinen, Petri; Voikar, Vootele; Chen, Alon; Erhardt, Angelika; Turck, Christoph W.; Hovatta, Iiris (26 September 2019).
388:
after normal development the disease usually begins late in the first year of life, although onset may occur in adulthood
3072:
2062:
716:
662:
2842:
956:, a poet, peace advocate, and motivational speaker who had dysautonomic mitochondrial myopathy, and who died at age 13.
441:
288:
86:
641:
2123:
Lorini & Ciman, M, & M (1962). "Hypoglycaemic action of
Diisopropylammonium salts in experimental diabetes".
897:
In June 2018 Australian Senate's Senate
Community Affairs References Committee recommended a move towards legalising
3258:
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3005:
359:
270:
248:
68:
46:
786:
3180:
628:
568:
has reported that cancer cells can hijack the mitochondria from immune cells via physical tunneling nanotubes.
1122:
Tsang SH, Aycinena AR, Sharma T (2018). "Mitochondrial disorder: maternally inherited diabetes and deafness".
152:
729:
504:
2571:
1958:
Petersen, Kitt Falk; Dufour, Sylvie; Befroy, Douglas; Garcia, Rina; Shulman, Gerald I. (12 February 2004).
1424:"Comprehensive summary of mitochondrial DNA alterations in the postmortem human brain: A systematic review"
3231:
2997:
1343:
Pieczenik, Steve R; Neustadt, John (2007). "Mitochondrial dysfunction and molecular pathways of disease".
748:
The glycogen generation capacity is entirely dependent on, and determined by, the operating levels of the
535:
520:
514:
474:
338:
221:
209:
168:
2265:
Marriage B, Clandinin MT, Glerum DM (2003). "Nutritional cofactor treatment in mitochondrial disorders".
846:
3045:
2436:
Tachibana M, Sparman M, Sritanaudomchai H, Ma H, Clepper L, Woodward J, Li Y, Ramsey C, Kolotushkina O,
2152:
2040:
963:
594:
217:
1301:"Mitochondrial dysfunction in bipolar disorder: Evidence from magnetic resonance spectroscopy research"
909:. The committee's report, released in July 2011, recommended the existing legislation remain unchanged
680:(all of which are encoded for by genes in the nuclear DNA) may also cause mitochondrial DNA mutations.
2534:
2453:
2348:
1960:"Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes"
1912:
891:
850:
765:
666:
558:
1899:, Neuenburg JK, Allen EA, Li GC, Klopstock T, Cowan TM, Enns GM, Davis RW (2009). Rzhetsky A (ed.).
3169:
2437:
295:
93:
2418:
2247:
1754:
1711:
1625:"Targeting tumor phenotypic plasticity and metabolic remodeling in adaptive cross-drug tolerance"
1476:"Multi-omics analysis identifies mitochondrial pathways associated with anxiety-related behavior"
1404:
1281:
982:, a nineteenth century naturalist who suffered from a disabling illness, is speculated to have
818:
reverses many models of mitochondrial dysfunction. In the case of mood disorders, specifically
571:
As a rule, mitochondrial diseases are worse when the defective mitochondria are present in the
3191:
2887:
2824:
2814:
2783:
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2518:
2479:
2410:
2374:
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2033:
2025:
1989:
1940:
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1803:
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1703:
1654:
1605:
1556:
1527:"Mitochondrial dysfunction in amyotrophic lateral sclerosis – a valid pharmacological target?"
1507:
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1145:
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generated by the mitochondria and the glycogen capacity is very loose and is mediated by many
688:
610:
351:
176:
1623:
Goldman A, Khiste S, Freinkman E, Dhawan A, Majumder B, Mondal J, et al. (August 2019).
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2017:
1979:
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1930:
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1793:
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1729:
Finsterer, Josef (2007). "Hematological
Manifestations of Primary Mitochondrial Disorders".
1693:
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The effective overall energy unit for the available body energy is referred to as the daily
525:
363:
181:
2523:"Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease"
1674:"Intercellular nanotubes mediate mitochondrial trafficking between cancer and immune cells"
17:
953:
677:
205:
1165:"Current and future landscape in genetic therapies for Leber hereditary optic neuropathy"
722:
A study by Yale University researchers (published in the February 12, 2004, issue of the
2698:
The Human Fertilisation and Embryology (Mitochondrial Donation) Regulations 2015 No. 572
2538:
2457:
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2037:
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1984:
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that generate energy for the cell and are found in every cell of the human body except
2278:
866:. A male baby was born in Mexico in 2016 from a mother with Leigh syndrome using MRT.
163:
showing ragged red fibers, a finding seen in various types of mitochondrial diseases.
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2136:
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1004:
930:
780:
673:
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164:
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have been proposed as a possible treatment for inherited mitochondrial disease, and
1901:"Mapping gene associations in human mitochondria using clinical disease phenotypes"
1126:. Advances in Experimental Medicine and Biology. Vol. 1085. pp. 163–165.
887:
871:
810:
are frequently prescribed, though the evidence for their effectiveness is limited.
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700:
658:
614:
478:
197:
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1269:
436:"Ragged Red Fibers" are clumps of diseased mitochondria that accumulate in the sub
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who had to retire from active play at age 29 due to mitochondrial channelopathy.
834:
708:
684:
637:
237:
35:
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2739:
2604:"Three parent baby law is 'irresponsible' says Church of England ahead of vote"
2313:
2021:
1689:
1591:
878:
government agreed to develop legislation that would legalize the 'three-person
2442:"Mitochondrial gene replacement in primate offspring and embryonic stem cells"
2100:
2083:
1848:"The maintenance of mitochondrial DNA integrity--critical analysis and update"
1640:
795:
757:
622:
540:
495:
Acquired conditions in which mitochondrial dysfunction has been involved are:
437:
421:
160:
2709:
2406:
1392:
3202:
2063:"David Keilin's respiratory chain concept and its chemiosmotic consequences"
606:
201:
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2828:
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2564:
2483:
2414:
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2235:
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1993:
1944:
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1707:
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region of the muscle fiber and appear when muscle is stained with modified
2207:
1317:
1300:
1181:
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of mitochondrial proteins as a radical treatment for mtDNA mutation load.
3226:
2906:
2769:
1975:
811:
741:
712:
704:
696:
583:, because these cells use more energy than most other cells in the body.
576:
499:
463:, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes
405:
355:
2546:
2499:"Scientists reveal gene-swapping technique to thwart inherited diseases"
2465:
1099:
1082:
1053:
1036:
807:
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Although research is ongoing, treatment options are currently limited;
3157:
1742:
1542:
3137:
3100:
2648:"Regulator to consult public over plans for new fertility treatments"
2360:
883:
761:
692:
572:
545:
509:
2843:"Young poet, peace advocate Mattie dies | the Spokesman-Review"
2586:"UK urged to permit IVF procedure to prevent fatal genetic diseases"
1081:
La Morgia C, Maresca A, Caporali L, Valentino ML, Carelli V (2020).
2810:
3207:
3086:
2623:"Exclusive: World's first baby born with new "3 parent" technique"
649:
627:
618:
580:
1218:. Handbook of Clinical Neurology. Vol. 194. pp. 43–63.
837:
is transferred to another healthy egg cell leaving the defective
2910:
3142:
2125:
Institute of Biochemistry, University of Padua, September 1962
1774:"Cerebellar Ataxia in Patients with Mitochondrial DNA Disease"
1163:
Shamsnajafabadi H, MacLaren RE, Cehajic-Kapetanovic J (2023).
879:
842:
550:
231:
29:
976:; decisions about his care were taken to various law courts.
683:
Most mitochondrial function and biogenesis is controlled by
2174:"Clinical pharmacology and toxicology of dichloroacetate"
1846:
Alexeyev M, Shokolenko I, Wilson G, LeDoux S (May 2013).
2754:"Mitochondrial Donation — How Many Women Could Benefit?"
2730:
The Daily Telegraph Science News, Retrieved 1 March 2014
2728:'Three-parent babies' could be born in Britain next year
1778:
Journal of Neuropathology & Experimental Neurology
1422:
Valiente-Pallejà, A; Tortajada, J; Bulduk, BK (2022).
903:
Prohibition of Human Cloning for Reproduction Act 2002
687:. Human mitochondrial DNA encodes 13 proteins of the
208:. They convert the energy of food molecules into the
3147:
2172:
Stacpoole PW, Henderson GN, Yan Z, James MO (1998).
397:
Neuropathy, ataxia, retinitis pigmentosa, and ptosis
3217:
3151:
3064:
3038:
2996:
2967:
2944:
949:Notable people with mitochondrial disease include:
481:
but are not associated with mitochondrial proteins.
262:. Unsourced material may be challenged and removed.
175:
142:
137:
60:. Unsourced material may be challenged and removed.
2395:Australian & New Zealand Journal of Psychiatry
2077:
2075:
1381:Australian & New Zealand Journal of Psychiatry
1672:Saha T, Dash C, Jayabalan R, et al. (2021).
814:has been proposed in 2007 as a treatment option.
2056:
2054:
402:progressive symptoms as described in the acronym
146:Mitochondrial cytopathy; mitochondriopathy (MCP)
2740:The Mitochondrial and Metabolic Disease Center
1076:
1074:
1072:
597:has sometimes been reported to be associated.
2922:
413:Myoneurogenic gastrointestinal encephalopathy
27:Disorders caused by mitochondrial dysfunction
8:
2157:: CS1 maint: multiple names: authors list (
1338:
1336:
1030:
1028:
1026:
1024:
385:, subacute necrotizing encephalomyelopathy
3148:
2929:
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2907:
1852:Cold Spring Harbor Perspectives in Biology
151:
134:
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2554:
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2099:
2094:(1). University of Alberta, 2007: 37–51.
1983:
1934:
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1871:
1797:
1697:
1648:
1599:
1576:"Mitochondria: in sickness and in health"
1550:
1501:
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1439:
1316:
1190:
1180:
1098:
1052:
907:Research Involving Human Embryos Act 2002
783:to detect large deletions or duplications
605:Mitochondrial disorders may be caused by
532:, aging and senescence, anxiety disorders
322:Learn how and when to remove this message
120:Learn how and when to remove this message
2224:Genetic Testing and Molecular Biomarkers
2131:(9). Biochemical Pharmacology: 823–827.
2337:"Mitochondria as a target in treatment"
996:
962:, a coach and former center fielder in
2710:"UK government backs three-person IVF"
2150:
2082:Michelakis, Evangelos (January 2007).
874:to have children. In June 2013, the
845:treatment procedure. Using a similar
7:
2803:Mitochondrial Replacement Techniques
1525:Muyderman, H; Chen, T (April 2014).
1345:Experimental and Molecular Pathology
974:mitochondrial DNA depletion syndrome
760:; however, the relation between the
648:typically contains between 2 and 10
467:Mitochondrial DNA depletion syndrome
260:adding citations to reliable sources
58:adding citations to reliable sources
1214:Rahman S (2023). "Leigh syndrome".
1124:Atlas of Inherited Retinal Diseases
1037:"Mitochondrial disease in children"
418:gastrointestinal pseudo-obstruction
371:Leber's hereditary optic neuropathy
1224:10.1016/B978-0-12-821751-1.00015-4
1083:"Mitochondrial diseases in adults"
192:is a group of disorders caused by
25:
3143:International Mito Patients (IMP)
2674:"Genetically altered babies born"
1574:Nunnari J, Suomalainen A (2012).
899:Mitochondrial replacement therapy
831:Mitochondrial replacement therapy
625:, or other environmental causes.
212:that powers most cell functions.
2621:Hamzelou, Jessica (2016-09-27).
2570:
826:Gene therapy prior to conception
236:
34:
3012:Mitochondrial encephalomyopathy
2858:"Charles Darwin's Mitochondria"
2758:New England Journal of Medicine
1964:New England Journal of Medicine
1531:British Journal of Pharmacology
1299:Stork, C; Renshaw, P F (2005).
725:New England Journal of Medicine
247:needs additional citations for
45:needs additional citations for
2726:Knapton, Sarah (1 March 2014)
2335:Frantz MC, Wipf P (Jun 2010).
433:progressive myoclonic epilepsy
345:diabetes mellitus and deafness
1:
2497:Boseley, Sarah (2010-04-14).
2279:10.1016/S0002-8223(03)00476-0
1270:10.1080/14789450.2021.1918550
886:mitochondrial transplant and
2137:10.1016/0006-2952(62)90177-6
1926:10.1371/journal.pcbi.1000374
1790:10.1097/NEN.0b013e318244477d
1493:10.1371/journal.pgen.1008358
1132:10.1007/978-3-319-95046-4_31
1087:Journal of Internal Medicine
1041:Journal of Internal Medicine
717:neurodevelopmental disorders
663:human mitochondrial genetics
609:(acquired or inherited), in
2874:10.1534/genetics.113.151241
1864:10.1101/cshperspect.a012641
1441:10.1016/j.ebiom.2022.103815
1357:10.1016/j.yexmp.2006.09.008
1258:Expert Review of Proteomics
18:Mitochondrial DNA Mutations
3280:
2646:Sample, Ian (2012-09-17).
2314:10.1016/j.mito.2007.07.002
2022:10.2337/diabetes.54.7.1926
1690:10.1038/s41565-021-01000-4
1592:10.1016/j.cell.2012.02.035
849:technique, researchers at
3117:
2856:Hayman, John (May 2013).
2101:10.1016/j.ccr.2006.10.020
1641:10.1126/scisignal.aas8779
1256:proteomics perspective".
787:Polymerase chain reaction
194:mitochondrial dysfunction
159:
150:
3107:Mohr–Tranebjærg syndrome
2407:10.1177/0004867412449303
2178:Environ. Health Perspect
1822:"Mitochondrial diseases"
1393:10.1177/0004867412449303
1005:"Mitochondrial Diseases"
972:, a British boy who had
860:from two different women
222:mitochondrial myopathies
3079:Kjer's optic neuropathy
2946:Carbohydrate metabolism
730:intramyocellular lipids
271:"Mitochondrial disease"
69:"Mitochondrial disease"
3264:Mitochondrial genetics
3254:Mitochondrial diseases
3122:mitochondrial proteins
2938:Mitochondrial diseases
2236:10.1089/gtmb.2019.0079
2190:10.1289/ehp.98106s4989
1216:Mitochondrial Diseases
634:
593:Cerebellar atrophy or
536:Cardiovascular disease
442:Gömöri trichrome stain
339:Mitochondrial myopathy
218:neuromuscular symptoms
169:Gomori trichrome stain
3134:Mitochondrial disease
2610:. London. 2015-04-30.
2592:. London. 2015-04-30.
2519:Turnbull, Douglass M.
2088:University of Alberta
1318:10.1038/sj.mp.4001711
1182:10.3390/cells12152013
964:Major League Baseball
631:
566:Nature Nanotechnology
491:Associated conditions
360:Kearns–Sayre syndrome
343:Maternally inherited
190:Mitochondrial disease
138:Mitochondrial disease
2770:10.1056/NEJMc1500960
1976:10.1056/NEJMoa031314
1305:Molecular Psychiatry
892:allotopic expression
851:Newcastle University
766:biochemical pathways
667:threshold expression
559:exercise intolerance
505:Huntington's disease
455:exercise intolerance
256:improve this article
54:improve this article
2547:10.1038/nature08958
2539:2010Natur.465...82C
2466:10.1038/nature08368
2458:2009Natur.461..367T
2353:2010EnvMM..51..462F
2341:Environ Mol Mutagen
2184:(Suppl 4): 989–94.
1917:2009PLSCB...5E0374S
847:pronuclear transfer
521:Parkinson's disease
515:Alzheimer's disease
475:Friedreich's ataxia
473:Conditions such as
3218:External resources
2440:(September 2009).
2068:. Nobel institute.
1731:Acta Haematologica
1434:(103815): 103815.
1100:10.1111/joim.13064
1054:10.1111/joim.13054
635:
3259:Molecular biology
3241:
3240:
3129:
3128:
3039:No primary system
2820:978-0-309-38870-2
2452:(7262): 367–372.
2061:Mitchell, Peter.
1743:10.1159/000105676
1629:Science Signaling
1543:10.1111/bph.12476
1141:978-3-319-95045-7
1035:Rahman S (2020).
855:Douglass Turnbull
839:mitochondrial DNA
833:(MRT), where the
816:N-acetyl cysteine
689:respiratory chain
611:mitochondrial DNA
352:diabetes mellitus
332:
331:
324:
306:
187:
186:
132:Medical condition
130:
129:
122:
104:
16:(Redirected from
3271:
3149:
3056:Pearson syndrome
2931:
2924:
2917:
2908:
2896:
2895:
2885:
2853:
2847:
2846:
2839:
2833:
2832:
2798:
2792:
2791:
2781:
2748:
2742:
2737:
2731:
2724:
2718:
2717:
2706:
2700:
2695:
2689:
2688:
2686:
2685:
2670:
2664:
2663:
2661:
2659:
2643:
2637:
2636:
2634:
2633:
2618:
2612:
2611:
2600:
2594:
2593:
2582:
2576:
2575:
2574:
2568:
2558:
2513:
2507:
2506:
2494:
2488:
2487:
2477:
2433:
2427:
2426:
2389:
2383:
2382:
2372:
2361:10.1002/em.20554
2332:
2326:
2325:
2297:
2291:
2290:
2262:
2256:
2255:
2218:
2212:
2211:
2201:
2169:
2163:
2162:
2156:
2148:
2120:
2114:
2113:
2103:
2079:
2070:
2069:
2067:
2058:
2049:
2048:
2016:(7): 1926–1933.
2004:
1998:
1997:
1987:
1955:
1949:
1948:
1938:
1928:
1905:PLOS Comput Biol
1892:
1886:
1885:
1875:
1843:
1837:
1836:
1834:
1832:
1818:
1812:
1811:
1801:
1769:
1763:
1762:
1726:
1720:
1719:
1701:
1678:Nat. Nanotechnol
1669:
1663:
1662:
1652:
1620:
1614:
1613:
1603:
1571:
1565:
1564:
1554:
1537:(8): 2191–2205.
1522:
1516:
1515:
1505:
1495:
1470:
1464:
1463:
1453:
1443:
1419:
1413:
1412:
1375:
1369:
1368:
1340:
1331:
1330:
1320:
1296:
1290:
1289:
1252:
1246:
1245:
1211:
1205:
1204:
1194:
1184:
1160:
1154:
1153:
1119:
1113:
1112:
1102:
1078:
1067:
1066:
1056:
1032:
1019:
1018:
1016:
1015:
1001:
820:bipolar disorder
791:mutation testing
526:Bipolar disorder
364:Pearson syndrome
327:
320:
316:
313:
307:
305:
264:
240:
232:
182:Medical genetics
155:
135:
125:
118:
114:
111:
105:
103:
62:
38:
30:
21:
3279:
3278:
3274:
3273:
3272:
3270:
3269:
3268:
3244:
3243:
3242:
3237:
3236:
3213:
3212:
3160:
3130:
3125:
3113:
3060:
3034:
2992:
2963:
2940:
2935:
2905:
2900:
2899:
2855:
2854:
2850:
2841:
2840:
2836:
2821:
2800:
2799:
2795:
2750:
2749:
2745:
2738:
2734:
2725:
2721:
2716:. 27 June 2013.
2708:
2707:
2703:
2696:
2692:
2683:
2681:
2672:
2671:
2667:
2657:
2655:
2645:
2644:
2640:
2631:
2629:
2620:
2619:
2615:
2602:
2601:
2597:
2584:
2583:
2579:
2569:
2533:(7294): 82–85.
2515:
2514:
2510:
2496:
2495:
2491:
2435:
2434:
2430:
2391:
2390:
2386:
2334:
2333:
2329:
2299:
2298:
2294:
2267:J Am Diet Assoc
2264:
2263:
2259:
2220:
2219:
2215:
2171:
2170:
2166:
2149:
2122:
2121:
2117:
2081:
2080:
2073:
2065:
2060:
2059:
2052:
2006:
2005:
2001:
1957:
1956:
1952:
1911:(4): e1000374.
1894:
1893:
1889:
1845:
1844:
1840:
1830:
1828:
1820:
1819:
1815:
1771:
1770:
1766:
1728:
1727:
1723:
1671:
1670:
1666:
1622:
1621:
1617:
1573:
1572:
1568:
1524:
1523:
1519:
1486:(9): e1008358.
1472:
1471:
1467:
1421:
1420:
1416:
1377:
1376:
1372:
1342:
1341:
1334:
1298:
1297:
1293:
1254:
1253:
1249:
1234:
1213:
1212:
1208:
1162:
1161:
1157:
1142:
1121:
1120:
1116:
1080:
1079:
1070:
1034:
1033:
1022:
1013:
1011:
1009:medlineplus.gov
1003:
1002:
998:
993:
954:Mattie Stepanek
947:
939:
929:and 800 in the
922:are very rare.
919:
828:
804:
774:
738:
678:DNA replication
652:copies. During
642:some exceptions
613:(mtDNA), or in
603:
493:
488:
477:can affect the
452:lactic acidosis
328:
317:
311:
308:
265:
263:
253:
241:
230:
206:red blood cells
133:
126:
115:
109:
106:
63:
61:
51:
39:
28:
23:
22:
15:
12:
11:
5:
3277:
3275:
3267:
3266:
3261:
3256:
3246:
3245:
3239:
3238:
3235:
3234:
3222:
3221:
3219:
3215:
3214:
3211:
3210:
3199:
3188:
3177:
3161:
3156:
3155:
3153:
3152:Classification
3146:
3145:
3140:
3127:
3126:
3118:
3115:
3114:
3112:
3111:
3110:
3109:
3097:
3096:
3095:
3093:HUPRA syndrome
3083:
3082:
3081:
3068:
3066:
3062:
3061:
3059:
3058:
3053:
3048:
3042:
3040:
3036:
3035:
3033:
3032:
3027:
3026:
3025:
3020:
3008:
3002:
3000:
2994:
2993:
2991:
2990:
2985:
2980:
2974:
2972:
2970:nervous system
2965:
2964:
2962:
2961:
2956:
2950:
2948:
2942:
2941:
2936:
2934:
2933:
2926:
2919:
2911:
2904:
2903:External links
2901:
2898:
2897:
2848:
2834:
2819:
2811:10.17226/21871
2805:. p. 37.
2793:
2764:(9): 885–887.
2743:
2732:
2719:
2701:
2690:
2665:
2638:
2613:
2595:
2577:
2508:
2489:
2428:
2384:
2327:
2308:(6): 399–401.
2292:
2273:(8): 1029–38.
2257:
2230:(3): 165–170.
2213:
2164:
2115:
2071:
2050:
1999:
1970:(7): 664–671.
1950:
1887:
1858:(5): a012641.
1838:
1813:
1764:
1721:
1664:
1615:
1586:(6): 1145–59.
1566:
1517:
1465:
1414:
1370:
1332:
1311:(10): 900–19.
1291:
1264:(4): 295–304.
1247:
1232:
1206:
1155:
1140:
1114:
1093:(6): 592–608.
1068:
1047:(6): 609–633.
1020:
995:
994:
992:
989:
988:
987:
984:MELAS syndrome
980:Charles Darwin
977:
967:
960:Rocco Baldelli
957:
946:
943:
938:
935:
927:United Kingdom
918:
915:
876:United Kingdom
864:ethical issues
841:behind, is an
827:
824:
803:
800:
799:
798:
793:
784:
773:
770:
752:in all of the
737:
734:
602:
599:
554:
553:
548:
543:
538:
533:
523:
518:
512:
507:
502:
492:
489:
487:
484:
470:
469:
464:
461:MELAS syndrome
458:
457:
456:
453:
450:
447:
444:
434:
429:MERRF syndrome
426:
425:
424:
419:
410:
409:
408:
403:
394:
393:
392:
389:
383:Leigh syndrome
380:
379:
378:
368:
367:
366:
341:
330:
329:
244:
242:
235:
229:
226:
185:
184:
179:
173:
172:
157:
156:
148:
147:
144:
140:
139:
131:
128:
127:
42:
40:
33:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
3276:
3265:
3262:
3260:
3257:
3255:
3252:
3251:
3249:
3233:
3229:
3228:
3224:
3223:
3220:
3216:
3209:
3205:
3204:
3200:
3198:
3194:
3193:
3189:
3187:
3183:
3182:
3178:
3176:
3172:
3171:
3167:
3163:
3162:
3159:
3154:
3150:
3144:
3141:
3139:
3135:
3132:
3131:
3124:
3123:
3116:
3108:
3105:
3104:
3103:
3102:
3098:
3094:
3091:
3090:
3089:
3088:
3084:
3080:
3077:
3076:
3075:
3074:
3070:
3069:
3067:
3063:
3057:
3054:
3052:
3049:
3047:
3044:
3043:
3041:
3037:
3031:
3028:
3024:
3021:
3019:
3016:
3015:
3014:
3013:
3009:
3007:
3004:
3003:
3001:
2999:
2995:
2989:
2986:
2984:
2981:
2979:
2978:Leigh disease
2976:
2975:
2973:
2971:
2966:
2960:
2957:
2955:
2952:
2951:
2949:
2947:
2943:
2939:
2932:
2927:
2925:
2920:
2918:
2913:
2912:
2909:
2902:
2893:
2889:
2884:
2879:
2875:
2871:
2867:
2863:
2859:
2852:
2849:
2844:
2838:
2835:
2830:
2826:
2822:
2816:
2812:
2808:
2804:
2797:
2794:
2789:
2785:
2780:
2775:
2771:
2767:
2763:
2759:
2755:
2747:
2744:
2741:
2736:
2733:
2729:
2723:
2720:
2715:
2711:
2705:
2702:
2699:
2694:
2691:
2679:
2675:
2669:
2666:
2653:
2649:
2642:
2639:
2628:
2627:New Scientist
2624:
2617:
2614:
2609:
2608:The Telegraph
2605:
2599:
2596:
2591:
2587:
2581:
2578:
2573:
2566:
2562:
2557:
2552:
2548:
2544:
2540:
2536:
2532:
2528:
2524:
2520:
2512:
2509:
2504:
2500:
2493:
2490:
2485:
2481:
2476:
2471:
2467:
2463:
2459:
2455:
2451:
2447:
2443:
2439:
2432:
2429:
2424:
2420:
2416:
2412:
2408:
2404:
2400:
2396:
2388:
2385:
2380:
2376:
2371:
2366:
2362:
2358:
2354:
2350:
2347:(5): 462–75.
2346:
2342:
2338:
2331:
2328:
2323:
2319:
2315:
2311:
2307:
2303:
2302:Mitochondrion
2296:
2293:
2288:
2284:
2280:
2276:
2272:
2268:
2261:
2258:
2253:
2249:
2245:
2241:
2237:
2233:
2229:
2225:
2217:
2214:
2209:
2205:
2200:
2195:
2191:
2187:
2183:
2179:
2175:
2168:
2165:
2160:
2154:
2146:
2142:
2138:
2134:
2130:
2126:
2119:
2116:
2111:
2107:
2102:
2097:
2093:
2089:
2085:
2078:
2076:
2072:
2064:
2057:
2055:
2051:
2046:
2042:
2039:
2035:
2031:
2027:
2023:
2019:
2015:
2011:
2003:
2000:
1995:
1991:
1986:
1981:
1977:
1973:
1969:
1965:
1961:
1954:
1951:
1946:
1942:
1937:
1932:
1927:
1922:
1918:
1914:
1910:
1906:
1902:
1898:
1891:
1888:
1883:
1879:
1874:
1869:
1865:
1861:
1857:
1853:
1849:
1842:
1839:
1827:
1823:
1817:
1814:
1809:
1805:
1800:
1795:
1791:
1787:
1784:(2): 148–61.
1783:
1779:
1775:
1768:
1765:
1760:
1756:
1752:
1748:
1744:
1740:
1736:
1732:
1725:
1722:
1717:
1713:
1709:
1705:
1700:
1695:
1691:
1687:
1684:(1): 98–106.
1683:
1679:
1675:
1668:
1665:
1660:
1656:
1651:
1646:
1642:
1638:
1634:
1630:
1626:
1619:
1616:
1611:
1607:
1602:
1597:
1593:
1589:
1585:
1581:
1577:
1570:
1567:
1562:
1558:
1553:
1548:
1544:
1540:
1536:
1532:
1528:
1521:
1518:
1513:
1509:
1504:
1499:
1494:
1489:
1485:
1481:
1480:PLOS Genetics
1477:
1469:
1466:
1461:
1457:
1452:
1447:
1442:
1437:
1433:
1429:
1425:
1418:
1415:
1410:
1406:
1402:
1398:
1394:
1390:
1386:
1382:
1374:
1371:
1366:
1362:
1358:
1354:
1350:
1346:
1339:
1337:
1333:
1328:
1324:
1319:
1314:
1310:
1306:
1302:
1295:
1292:
1287:
1283:
1279:
1275:
1271:
1267:
1263:
1259:
1251:
1248:
1243:
1239:
1235:
1233:9780128217511
1229:
1225:
1221:
1217:
1210:
1207:
1202:
1198:
1193:
1188:
1183:
1178:
1174:
1170:
1166:
1159:
1156:
1151:
1147:
1143:
1137:
1133:
1129:
1125:
1118:
1115:
1110:
1106:
1101:
1096:
1092:
1088:
1084:
1077:
1075:
1073:
1069:
1064:
1060:
1055:
1050:
1046:
1042:
1038:
1031:
1029:
1027:
1025:
1021:
1010:
1006:
1000:
997:
990:
985:
981:
978:
975:
971:
968:
965:
961:
958:
955:
952:
951:
950:
945:Notable cases
944:
942:
936:
934:
932:
931:United States
928:
923:
916:
914:
910:
908:
904:
900:
895:
893:
889:
885:
881:
877:
873:
867:
865:
861:
856:
852:
848:
844:
840:
836:
832:
825:
823:
821:
817:
813:
809:
801:
797:
794:
792:
789:and specific
788:
785:
782:
781:Southern blot
779:
778:
777:
771:
769:
767:
763:
759:
755:
751:
746:
743:
735:
733:
731:
727:
726:
720:
718:
714:
710:
706:
702:
698:
694:
690:
686:
681:
679:
675:
674:Mutation rate
670:
668:
664:
660:
655:
654:cell division
651:
647:
646:mitochondrion
643:
639:
630:
626:
624:
620:
616:
615:nuclear genes
612:
608:
600:
598:
596:
591:
588:
584:
582:
578:
574:
569:
567:
562:
560:
552:
549:
547:
544:
542:
539:
537:
534:
531:
530:schizophrenia
527:
524:
522:
519:
516:
513:
511:
508:
506:
503:
501:
498:
497:
496:
490:
485:
483:
482:
480:
476:
468:
465:
462:
459:
454:
451:
448:
446:short stature
445:
443:
439:
435:
432:
431:
430:
427:
423:
420:
417:
416:
414:
411:
407:
404:
401:
400:
398:
395:
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