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A history of mitochondrial diseases

  • Mitochondrial Medicine
  • Published:
Journal of Inherited Metabolic Disease

Abstract

This articles reviews the development of mitochondrial medicine from the premolecular era (1962–1988), when mitochondrial diseases were defined on the basis of clinical examination, muscle biopsy, and biochemical criteria, through the molecular era, when the full complexity of these disorders became evident. In a chronological order, I have followed the introduction of new pathogenic concepts that have shaped a rational genetic classification of these clinically heterogeneous disorders. Thus, mitochondrial DNA (mtDNA)-related diseases can be divided into two main groups: those that impair mitochondrial protein synthesis in toto, and those that affect specific respiratory chain proteins. Mutations in nuclear DNA can affect components of respiratory chain complexes (direct hits) or assembly proteins (indirect hits), but they can also impair mtDNA integrity (multiple mtDNA mutations), replication (mtDNA depletion), or mtDNA translation. Besides these disorders that affect the respiratory chain directly, defects in other mitochondrial functions may also affect oxidative phosphorylation, including problems in mitochondrial protein import, alterations of the inner mitochondrial membrane lipid composition, and defects of mitochondrial dynamics. The enormous and still ongoing progress in our understanding of mitochondrial medicine was made possible by the intense collaboration of an international cadre of “mitochondriacs.” Having published my first paper on a patient with mitochondrial myopathy 37 years ago (DiMauro et al., 1973), I feel qualified to write a history of the mitochondrial diseases, a fascinating, still evolving, and continuously puzzling area of medicine. In each section, I follow a chronological order of the salient discoveries and I show only the portraits of distinguished deceased mitochondriacs and those whose names became eponyms of mitochondrial diseases.

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References

  • Alexander C, Votruba M, Pesch UEA, Thiselton DL, Mayer S, Moore A et al (2000) OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat Genet 26:211–215

    Article  PubMed  CAS  Google Scholar 

  • Amati-Bonneau P, Valentino ML, Reynier P, Gallardo ME, Bornstein B, Boissiere A et al (2008) OPA1 mutations induce mitochondrial DNA instability and optic atrophy “plus” phenotypes. Brain 131:338–351

    Article  PubMed  Google Scholar 

  • Antonicka H, Mattman A, Carlson CG, Glerum DM, Hoffbuhr KC, Leary SC et al (2003) Mutations in COX15 produce a defect in the mitochondrial heme biosynthetic pathway, causing early-onset fatal hypertrophic cardiomyopathy. Am J Hum Genet 72:101–114

    Article  PubMed  CAS  Google Scholar 

  • Antonicka H, Sasarman F, Kennaway NG, Shoubridge EA (2006) The molecular basis for tissue specificity of the oxidative phosphorylation deficiencies in patients with mutations in the mitochondrial translation factor EFG1. Hum Mol Genet 15:1835–1846

    Article  PubMed  CAS  Google Scholar 

  • Area-Gomez E, de Groof AJC, Boldogh I, Bird TD, Gibson GE, Koehler CM et al (2009) Presenilins are enriched in mitochondria-associated membranes. Am J Pathol 175:1810–1818

    Article  PubMed  CAS  Google Scholar 

  • Auré K, Benoist JF, de Ogier Baulny H, Romero NB, Rigal O, Lombes A (2004) Progression despite replacement of a myopathic form of coenzyme Q10 defect. Neurology 63:727–729

    PubMed  Google Scholar 

  • Bardosi A, Creutzfeldt W, DiMauro S, Felgenhauer K, Friede RL, Goebel HH et al (1987) Myo-, neuro-, gastrointestinal encephalopathy (MNGIE syndrome) due to partial deficiency of cytochrome-c-oxidase. A new mitochondrial multisystem disorder. Acta Neuropathol 74:248–258

    Article  PubMed  CAS  Google Scholar 

  • Barth PG, Scholte HR, Berden JA, Moorsel V, Luyt-Houwen I, Van’t Veer-Korthof ET et al (1983) An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes. J Neurol Sci 62:327–355

    Article  PubMed  CAS  Google Scholar 

  • Bione S, D'Adamo P, Maestrini E, Gedeon AK, Bolhuis PA, Toniolo D (1996) A novel X-linked gene, G4.5, is responsible for Barth syndrome. Nat Genet 12:385–389

    Article  PubMed  CAS  Google Scholar 

  • Blass JP, Avigan J, Uhlendorf BW (1970) A defect in pyruvate decarboxylase in a child with an intermittent movement disorder. J Clin Invest 49:423–432

    Article  PubMed  CAS  Google Scholar 

  • Bolender N, Sickmann A, Wagner R, Meisinger C, Pfanner N (2008) Multiple pathways for sorting mitochondrial precursor proteins. EMBO J 9:42–49

    Article  CAS  Google Scholar 

  • Bonilla E, Sciacco M, Tanji K, Sparaco M, Petruzzella V, Moraes CT (1992) New morphological approaches to the study of mitochondrial encephalomyopathies. Brain Pathol 2:113–119

    Article  PubMed  CAS  Google Scholar 

  • Bossy-Wetzel E, Barsoum MJ, Godzik A, Schwartzenbacher R, Lipton SA (2003) Mitochondrial fission in apoptosis, neurodegeneration and aging. Curr Opin Cell Biol 15:706–716

    Article  PubMed  CAS  Google Scholar 

  • Bourgeron T, Rustin P, Chretien D, Birch-Machin M, Bourgeois M, Viegas-Pequignot E et al (1995) Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nat Genet 11:144–149

    Article  PubMed  CAS  Google Scholar 

  • Bykhovskaya Y, Casas KA, Mengesha E, Inbal A, Fischel-Ghodsian N (2004) Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA). Am J Hum Genet 74:1303–1308

    Article  PubMed  CAS  Google Scholar 

  • Cao L, Shitara H, Sugimoto M, Hayashi J-I, Abe K, Yonekawa H (2009) New evidence confirms that the mitochondrial bottleneck is generated without reduction of mitochondrial DNA content in early primordial germ cells of mice. PloS Genetics 5(12):e1000756

    Article  CAS  Google Scholar 

  • Carelli V, Barboni P, Sadun AA (2006) Mitochondrial ophthalmology. In: DiMauro S, Hirano M, Schon EA (eds) Mitochondrial medicine. Informa Healthcare, London, pp 105–142

    Google Scholar 

  • Chan DC (2006) Mitochondria: dynamic organelles in disease, aging, and development. Cell 125:1241–1252

    Article  PubMed  CAS  Google Scholar 

  • Chan DC (2007) Mitochondrial dynamics in disease. New Engl J Med 356:1707–1709

    Article  PubMed  CAS  Google Scholar 

  • Chinnery PF, Taylor DJ, Brown DT, Manners D, Styles P, Lodi R (2000) Very low levels of the mtDNA A3243G mutation associated with mitochondrial dysfunction in vivo. Ann Neurol 47:381–384

    Article  PubMed  CAS  Google Scholar 

  • Chomyn A, Enriquez JA, Micol V, Fernandez-Silva P, Attardi G (2000) The mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode syndrome-associated human mitochondrial tRNALeu(UUR) mutation causes aminoacylation deficiency and concomitant reduced association of mRNA with ribosomes. J Biol Chem 275:19198–19209

    Article  PubMed  CAS  Google Scholar 

  • Cizkova A, Stranecky V, Mayr JA, Tesarova M, Havlikova V, Paul J et al (2009) TMEM70 mutations cause isolated ATP synthase deficiency and eonatal mitochondrial encephalomyopathy. Nat Genet 40:12881290

    Google Scholar 

  • Coenen MJH, Antonicka H, Ugalde C, Sasarman F, Rossi P, Heister JGAMA et al (2004) Mutant mitochondrial elongation factor G1 and combined oxidative phosphorylation deficiency. New Engl J Med 351:2080–2086

    Article  PubMed  CAS  Google Scholar 

  • Cree LM, Samuels DC, de Sousa Lopes SC, Rajasimha HK, Wonnapinij P, Mann JR et al (2008) A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes. NatGenet 40:249–254

    CAS  Google Scholar 

  • Darin N, Oldfors A, Moslemi A-R, Holme E, Tulinius M (2001) The incidence of mitochondrial encephalomyopathies in childhood: clinical features and morphological, biochemical, and DNA abnormalities. Ann Neurol 49:377–383

    Article  PubMed  CAS  Google Scholar 

  • Davey KM, Parboosingh JS, McLeaod DR, Chan A, Casey R, Ferreira P et al (2006) Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-kike condition. J Med Genet 43:385–393

    Article  PubMed  CAS  Google Scholar 

  • De Meirleir L, Seneca S, Lissens W, De Clercq I, Eyskens F, Gerlo E et al (2004) Respiratory chain complex V deficiency due to a mutation in the assembly gene ATP12. J Med Genet 41:120–124

    Article  PubMed  CAS  Google Scholar 

  • DeFrancesco L, Scheffler IE, Bissell MJ (1976) A respiration-deficient Chinese hamster cell line with a defect in NADH-coenzyme Q reductase. J Biol Chem 251:4588–4595

    PubMed  CAS  Google Scholar 

  • Dejardins P, Frost E, Morais R (1985) Ethidium bromide-induced loss of mitochondrial DNA from primary chicken embryo fibroblasts. Mol Cell Biol 5:1163–1169

    Google Scholar 

  • Delettre C, Lenaers G, Griffoin J-M, Gigarel N, Lorenzo C, Belenguer P et al (2000) Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet 26:207–210

    Article  PubMed  CAS  Google Scholar 

  • DiMauro S, DiMauro-Melis PM (1973) Muscle carnitine palmityltransferase deficiency and myoglobinuria. Science 182:929–931

    Article  PubMed  CAS  Google Scholar 

  • DiMauro S, Schon EA (2008) Mitochondrial disorders in the nervous system. Annu Rev Neurosci 31:91–123

    Article  PubMed  CAS  Google Scholar 

  • DiMauro S, Hirano M, Schon EA (eds) (2006) Mitochondrial medicine. Informa Healthcare, Abingdon

    Google Scholar 

  • DiMauro S, Bonilla E, Zeviani M, Nakagawa M, DeVivo DC (1985) Mitochondrial myopathies. Ann Neurol 17:521–538

    Article  PubMed  CAS  Google Scholar 

  • DiMauro S, Schotland DL, Bonilla E, Lee CP, Gambetti PL, Rowland LP (1973) Progressive ophthalmoplegia, glycogen storage, and abnormal mitochondria. Arch Neurol 29:170–179

    PubMed  CAS  Google Scholar 

  • Dimauro S, Bonilla E, Lee CP, Schotland DL, Scarpa A, Conn H et al (1976) Luft's disease. Further biochemical and ultrastructural studies of skeletal muscle in the second case. J Neurol Sci 27:217–232

    Article  PubMed  CAS  Google Scholar 

  • Diomedi-Camassei F, Di Giandomenico S, Santorelli F, Caridi G, Piemonte F, Montini G et al (2007) COQ2 nephropathy: a newly described inherited mitochondriopathy with primary renal involvement. J Am Soc Nephrol 18:2773–2780

    Article  PubMed  CAS  Google Scholar 

  • Dubeau F, De Stefano N, Zifkin BG, Arnold DL, Shoubridge EA (2000) Oxidative phosphorylation defect in the brains of carriers of the tRNAleu (UUR) A3243G mutation in a MELAS pedigree. Ann Neurol 47:179–185

    Article  PubMed  CAS  Google Scholar 

  • Duncan AJ, Bitner-Glindziez M, Meunier B, Costello H, Hargreaves IP, Lopez LC et al (2009) A nonsense mutation in COQ9 causes autosomal recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease. Am J Hum Genet 84:558–566

    Article  PubMed  CAS  Google Scholar 

  • Edvarson S, Shaag A, Kolesnikova O, Gomori JM, Tarassov I, Einbinder T et al (2007) Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia. Am J Hum Genet 81:857–862

    Article  CAS  Google Scholar 

  • Elliott HR, Samuels DC, Eden JA, Relton CL, Chinnery PF (2008) Pathogenic mitochondrial DNA mutations are common in the general population. Am J Hum Genet 83:254–260

    Article  PubMed  CAS  Google Scholar 

  • Engel AG, Angelini C (1973) Carnitine deficiency of human skeletal muscle with associated lipid storage myopathy: a new syndrome. Science 179:899–902

    Article  PubMed  CAS  Google Scholar 

  • Engel WK, Cunningham CG (1963) Rapid examination of muscle tissue: an improved trichrome stain method for fresh-frozen biopsy sections. Neurology 13:919–923

    PubMed  CAS  Google Scholar 

  • Fenton WA (1995) Mitochondrial protein transport-a system in search of mutations. Am J Hum Genet 57:235–238

    PubMed  CAS  Google Scholar 

  • Fichera M, Lo Giudice M, Falco M, Sturnio M, Amata A, Calabrese O et al (2004) Evidence of kinesin heavy chain (KIF5A) involvement in pure hereditary spastic paraplegia. Neurology 63:1108–1110

    PubMed  CAS  Google Scholar 

  • Filosto M, Mancuso M, Vives-Bauza C, Vila MR, Shanske S, Hirano M et al (2003) Lack of paternal inheritance of muscle mitochondrial DNA in sporadic mitochondrial myopathies. Ann Neurol 54:524–526

    Article  PubMed  CAS  Google Scholar 

  • Fukuhara N, Tokiguchi S, Shirakawa K, Tsubaki T (1980) Myoclonus epilepsy associated with ragged-red fibers (mitochondrial abnormalities): disease entity or a syndrome? J Neurol Sci 47:117–133

    Article  PubMed  CAS  Google Scholar 

  • Gempel K, Topaloglu H, Talim B, Schneiderat P, Schoser BGH, Hans VH et al (2007) The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene. Brain 130:2037–2044

    Article  PubMed  Google Scholar 

  • Ghezzi D, Goffrini P, Uziel G, Horvath R, Klopstock T, Lochmuller H et al (2009) SDHAF1, encoding a LYR complex II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy. Nat Genet 41:654–656

    Article  PubMed  CAS  Google Scholar 

  • Gironi M, Lamperti C, Nemni R, Moggio M, Comi GP, Guerini FR et al (2004) Late-onset cerebellar ataxia with hypogonadism and muscle coenzyme Q10 deficiency. Neurology 62:818–820

    PubMed  CAS  Google Scholar 

  • Gonatas NK, Shy GM (1965) Childhood myopathies with abnormal mitochondria. Proceedings of the Vth International Congress of Neuropathology Vol 100. Excerpta Medica International Congress Series, Amsterdam, pp 606–612

    Google Scholar 

  • Goto Y, Nonaka I, Horai S (1990) A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 348:651–653

    Article  PubMed  CAS  Google Scholar 

  • Greaves LC, Preston SL, Tadrous PJ, Taylor RW, Barron MJ, Oukrif D, Leedham SJ et al (2006) Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by cryptic fission. Proc Natl Acad Sci USA 103:714–719

    Article  PubMed  CAS  Google Scholar 

  • Guan M-X, Yan Q, Li X, Bykhovskaya Y, Gallo-Teran J, Hajek P et al (2006) Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitochondrial 12 S ribosomal RNA mutations. Am J Hum Genet 79:291302

    Article  Google Scholar 

  • Hakonen AH, Heiskanen S, Juvonen V, Lappalainen I, Luoma P, Rantamaki M et al (2005) Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin. Am J Hum Genet 77:430–441

    Article  PubMed  CAS  Google Scholar 

  • Hansen JJ, Durr A, Cournu-Rebeix I, Georgopoulos C, Ang D, Nyholm Nielsen M et al (2002) Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. Am J Hum Genet 70(5):1328–1332

    Google Scholar 

  • Haut S, Brivet M, Tonati G, Rustin P, Lebon S, Garcia-Cazorla A et al (2003) A deletion in the human QP-C gene causes a complex III deficiency resulting in hypoglycaemia and lactic acidosis. Hum Genet 113:118–122

    PubMed  CAS  Google Scholar 

  • Haydar NA, Conn HL, Afifi A, Wakid N, Ballas S, Fawaz K (1971) Severe hypermetabolism with primary abnormality of skeletal muscle mitochondria. Ann Int Med 74:548–558

    PubMed  CAS  Google Scholar 

  • Hers HG (1965) Inborn lysosomal diseases. Gastroenterol 48:625–633

    CAS  Google Scholar 

  • Hinson JT, Fantin VR, Schonberger J, Breivik N, Siem G, McDonough B et al (2007) Missense mutations in the BCS1L gene as a cause of the Bjornstad syndrome. New Engl J Med 356:809–819

    Article  PubMed  CAS  Google Scholar 

  • Hirano M, Silvestri G, Blake D, Lombes A, Minetti C, Bonilla E et al (1994) Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical, biochemical and genetic features of an autosomal recessive mitochondrial disorder. Neurology 44:721–727

    PubMed  CAS  Google Scholar 

  • Hirano M, Garcia-de-Yebenes J, Jones AC, Nishino I, DiMauro S, Carlo JR et al (1998) Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) syndrome maps to chromosome 22q13.32-qter. Am J Hum Genet 63:526–533

    Article  PubMed  CAS  Google Scholar 

  • Hirano M, Marti R, Casali C, Tadesse BS, Uldrick T, Fine B et al (2006) Allogeneic stem cell transplantation corrects biochemical derangements in MNGIE. Neurology 67:1458–1460

    Article  PubMed  CAS  Google Scholar 

  • Holt IJ, Harding AE, Morgan Hughes JA (1988) Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331:717–719

    Article  PubMed  CAS  Google Scholar 

  • Holt IJ, Harding AE, Petty RK, Morgan Hughes JA (1990) A new mitochondrial disease associated with mitochondrial DNA heteroplasmy. Am J Hum Genet 46:428–433

    PubMed  CAS  Google Scholar 

  • Horvath R, Hudson G, Ferrari G, Futterer N, Ahola S, Lamantea E et al (2006) Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene. Brain 129:1674–1684

    Article  PubMed  Google Scholar 

  • Horvath R, Kemp JP, Tuppen HAL, Hudson G, Oldfors A, Marie SKN et al (2009) Molecular basis of infantile reversible cytochrome c oxidase deficiency. Brain 132:3165–3174

    Article  PubMed  Google Scholar 

  • Hudson G, Keers S, Man PYW, Griffiths P, Huoponen K, Savontaus M-L et al (2005) Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder. Am J Hum Genet 77:1086–1091

    Article  PubMed  CAS  Google Scholar 

  • Hudson G, Carelli V, Spruijt L, Gerards M, Mowbray C, Achilli A et al (2007) Clinical expression of leber hereditary optic neuropahy is affected by the mitochondrial DNA-haplogroup background. Am J Hum Genet 81:228–233

    Article  PubMed  CAS  Google Scholar 

  • Hudson G, Amati-Bonneau P, Blakely E, Stewart JD, He L, Schaefer AM et al (2008) Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance. Brain 131:329–337

    Article  PubMed  Google Scholar 

  • Jacobs HT, Turnbull DM (2005) Nuclear genes and mitochondrial translation: a new class of genetic disease. Trends Genet 21:312–314

    Article  PubMed  CAS  Google Scholar 

  • Jenuth JP, Peterson AC, Fu K, Shoubridge EA (1996) Random genetic drift in the female germline explains the rapid segregation of mammalian mitochondrial DNA. Nat Genet 14:146–151

    Article  PubMed  CAS  Google Scholar 

  • Kadowaki T, Kadowaki H, Mori Y, Tobe K, Sakuta R, Suzuki Y et al (1994) A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA. New Engl J Med 330:962–968

    Article  PubMed  CAS  Google Scholar 

  • Karadimas CL, Vu TH, Holve SA, Quinzii C, Tanji K, Bonilla E et al (2006) Navajo neurohepatopathy is caused by a mutation in the MPV17 gene. Am J Hum Genet 79:544–548

    Article  PubMed  CAS  Google Scholar 

  • Karpati G, Carpenter S, Engel AG (1975) The syndrome of systemic carnitine deficiency. Neurology 25:16–24

    PubMed  CAS  Google Scholar 

  • Kaufmann P, Shungu D, Sano MC, Jhung S, Engelstad K, Mitsis E et al (2004) Cerebral lactic acidosis correlates with neurological impairment in MELAS. Neurology 62:1297–1302

    PubMed  CAS  Google Scholar 

  • Kaukonen J, Juselius JK, Tiranti V, Kyttala A, Zeviani M, Comi GP et al (2000) Role of adenine nucleotide translocator 1 in mtDNA maintenance. Science 289:782–785

    Article  PubMed  CAS  Google Scholar 

  • King MP, Attardi G (1989) Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science 246:500–503

    Article  PubMed  CAS  Google Scholar 

  • King MP, Koga Y, Davidson M, Schon EA (1992) Defects in mitochondrial protein synthesis and respiratory chain activity segragate with the tRNALeu(UUR) mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. Mol Cell Biol 12:480–490

    PubMed  CAS  Google Scholar 

  • Kirby DM, Salemi R, Sugiana C, Ohtake A, Parry L, Bell KM et al (2004) NUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency. J Clin Invest 114:837–845

    PubMed  CAS  Google Scholar 

  • Kraytsberg Y, Schwartz M, Brown TA, Ebralidse K, Kunz WS, Clayton DA et al (2004) Recombination of human mitochondrial DNA. Science 304:981

    Article  PubMed  CAS  Google Scholar 

  • Lagier-Tourenne C, Tazir M, Lopez LC, Quinzii C, Assoum M, Drouot N et al (2008) ADSK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency. Am J Hum Genet 82:661–672

    Article  PubMed  CAS  Google Scholar 

  • Lalani S, Vladutiu GD, Plunkett K, Lotze TE, Adesina AM, Scaglia F (2005) Isolated mitochondrial myopathy associated with muscle coenzyme Q10 deficiency. Arch Neurol 62:317–320

    Article  PubMed  Google Scholar 

  • Lamperti C, Naini A, Hirano M, De Vivo DC, Bertini E, Servidei S et al (2003) Cerebellar ataxia and coenzyme Q10 deficiency. Neurology 60:1206–1208

    PubMed  CAS  Google Scholar 

  • Ledley FD, Jansen R, Nham SU, Fenton WA, Rosenberg LE (1990) Mutation eliminating mitochondrial leader sequence of methylmalonyl-CoA mutase causes mut0 methylmalonic acidemia. Proc Natl Acad Sci USA 87:3147–3150

    Article  PubMed  CAS  Google Scholar 

  • Lestienne P, Ponsot G (1988) Kearns-Sayre syndrome with muscle mitochondrial DNA deletion. Lancet 1:885

    Article  PubMed  CAS  Google Scholar 

  • Lopez LC, Quinzii C, Schuelke M, Kanki T, Naini A, DiMauro S et al (2006) Leigh syndrome with nephropathy and CoQ10 deficiency due to decaproneyl diphosphate synthase subunit 2 (PDSS2) mutations. Am J Hum Genet 79:1125–1129

    Article  PubMed  CAS  Google Scholar 

  • Luft R, Ikkos D, Palmieri G, Ernster L, Afzelius B (1962) A case of severe hypermetabolism of nonthyroid origin with a defect in the maintenance of mitochondrial respiratory control: a correlated clinical, biochemical, and morphological study. J Clin Invest 41:1776–1804

    Article  PubMed  CAS  Google Scholar 

  • Magen D, Georgopoulos C, Bross P, Ang D, Segev Y, Goldsher D et al (2008) Mitochondrial Hsp60 chaperonopathy causes an autosomal-recessive neurodegenerative disorder linked to brain hypomyelination and leukodystrophy. Am J Hum Genet 83:30–42

    Article  PubMed  CAS  Google Scholar 

  • Mangiullo R, Gnoni A, Leone A, Gnoni GV, Papa S, Zanotti F (2008) Structural and functional characterization of F0F1-ATP synthase on the extracellular surface of rat hepatocytes. Biochim Biophys Acta 1777:1326–1335

    Article  PubMed  CAS  Google Scholar 

  • Manwaring N, Jones MM, Wang JJ, Rochtchina E, Howard C, Mitchell P et al (2007) Population prevalence of the MELAS A3243G mutation. Mitochondrion 7:230–233

    Article  PubMed  CAS  Google Scholar 

  • Marti R, Nishigaki Y, Hirano M (2003) Elevated plasma deoxyuridine in patients with thymidine phosphorylase deficiency. Biochem Biophys Res Comm 303:14–18

    Article  PubMed  CAS  Google Scholar 

  • Massa V, Fernandez-Vizarra E, Alshahwan S, Bakhsh E, Goffrini P, Ferrero I et al (2008) Severe infantile encephalomyopathy caused by a mutation in COX6B1, a nucleus-encoded subunit of cytochrome c oxidase. Am J Hum Genet. doi:10.1016/j.ajhg.2008.05.002

    PubMed  Google Scholar 

  • Masucci JP, Davidson M, Koga Y, Schon EA, King MP (1995) In vitro analysis of mutations causing myoclonus epilepsy with ragged-red fibers in the mitochondrial tRNALys gene: two genotypes produce similar phenotypes. Mol Cell Biol 15:2872–2881

    PubMed  CAS  Google Scholar 

  • McKenzie M, Lazarou M, Thorburn DR, Ryan MT (2006) Mitochondrial respiratory chain supercomplexes are destabilized in Barth syndrome patients. J Mol Biol 361:462–469

    Article  PubMed  CAS  Google Scholar 

  • Miller C, Saada A, Shaul N, Shabtai N, Ben-Shalom E, Shaag E et al (2004) Defective mitochondrial translation caused by a ribosomal protein (MRPS16) mutation. Ann Neurol 56:734–738

    Article  PubMed  CAS  Google Scholar 

  • Mollet J, Giurgea I, Schlemmer D, Dallner G, Chretien D, Delahodde A et al (2007) Prenyldiphosphate synthase (PDSS1) and OH-benzoate prenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders. J Clin Invest 117:765–772

    Article  PubMed  CAS  Google Scholar 

  • Mollet J, Delahodde A, Serre V, Chretien D, Schlemmer D, Lombes A et al (2008) CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia and seizures. Am J Hum Genet 82:623–630

    Article  PubMed  CAS  Google Scholar 

  • Mootha VK, Lepage P, Miller K, Bunkenborg J, Reich M, Hjerrild M et al (2003) Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics. Proc Natl Acad Sci USA 100:605–610

    Article  PubMed  CAS  Google Scholar 

  • Moraes CT, DiMauro S, Zeviani M, Lombes A, Shanske S, Miranda AF et al (1989) Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome `see comments. N Engl J Med 320:1293–1299

    Article  PubMed  CAS  Google Scholar 

  • Moraes CT, Shanske S, Tritschler HJ, Aprille JR, Andreetta F, Bonilla E et al (1991) MtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases. Am J Hum Genet 48:492–501

    PubMed  CAS  Google Scholar 

  • Moraes CT, Ricci E, Bonilla E, DiMauro S, Schon EA (1992) The mitochondrial tRNALeu(UUR) mutation in mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS): genetic, biochemical, and morphological correlations in skeletal muscle. Am J Hum Genet 50:934–949

    PubMed  CAS  Google Scholar 

  • Morais R, Desjardins P, Turmel C, Zinkewich-Peotti K (1988) Development and characterization of continuous avian cell lines depleted of mitochondrial DNA. In Vitro Cell Dev Biol 24:649–658

    Article  PubMed  CAS  Google Scholar 

  • Musumeci O, Naini A, Slonim AE, Scavin N, Hadjigeorgiou GL, Krawiecki N et al (2001) Familial cerebellar ataxia with muscle coenzyme Q10 deficiency. Neurology 56:849–855

    PubMed  CAS  Google Scholar 

  • Nass MMK, Nass S (1963a) fibers with DNA characteristics. I. Fixation and electron staining reactions. J Cell Biol 19:593–612

    Article  PubMed  CAS  Google Scholar 

  • Nass S, Nass M (1963b) Intramitochondrial fibers with DNA characteristics. II. Enzymatic and other hydrolytic treatments. J Cell Biol 19:613–629

    Article  PubMed  CAS  Google Scholar 

  • Naviaux RK, Nguyen KV (2004) POLG mutations associated with Alpers′ syndrome and mitochondrial DNA depletion. Ann Neurol 55:706–712

    Article  PubMed  CAS  Google Scholar 

  • Naviaux RK, Nyhan WL, Barshop BA, Poulton J, Markusic D, Karpinski NC et al (1999) Mitochondrial DNA polymerase gamma deficiency and mtDNA depletion in a child with Alpers′ syndrome. Ann Neurol 45:54–58

    Article  PubMed  CAS  Google Scholar 

  • Nishigaki Y, Marti RA, Copeland WC, Hirano M (2003) Site-specific somatic mitochondrial DNA point mutations in patients with thymidine phosphorylase deficiency. J Clin Invest 111:1913–1921

    PubMed  CAS  Google Scholar 

  • Nishino I, Spinazzola A, Hirano M (1999) Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 283:689–692

    Article  PubMed  CAS  Google Scholar 

  • Ogasahara S, Engel AG, Frens D, Mack D (1989) Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy. Proc Natl Acad Sci USA 86:2379–2382

    Article  PubMed  CAS  Google Scholar 

  • Ogilvie I, Kennaway NG, Shoubridge EA (2005) A molecular chaperone for mitochondrial complex I assembly is mutated in a progressive encephalopathy. J Clin Invest 115:2784–2792

    Article  PubMed  CAS  Google Scholar 

  • Papadopoulou LC, Sue CM, Davidson MM, Tanji K, Nishino I, Sadlock JE et al (1999) Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene. Nat Genet 23:333–337

    Article  PubMed  CAS  Google Scholar 

  • Pavlakis SG, Phillips PC, DiMauro S, De Vivo DC, Rowland LP (1984) Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome. Ann Neurol 16:481–488

    Article  PubMed  CAS  Google Scholar 

  • Petty RK, Harding AE, Morgan Hughes JA (1986) The clinical features of mitochondrial myopathy. Brain 109:915–938

    Article  PubMed  Google Scholar 

  • Poulton J, Hirano M, Spinazzola A, Arenas Hernandez M, Jardel C, Lombes A et al (2009) Collated mutations in mitochondrial DNA (mtDNA) depletion syndrome (excludingbthe mitochondrial gamma polymerase, POLG1). Biochim Biophys Acta 1792:1109–1112

    PubMed  CAS  Google Scholar 

  • Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu W-Q et al (1993) Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat Genet 4:289–293

    Article  PubMed  CAS  Google Scholar 

  • Quinzii C, Kattah AG, Naini A, Akman HO, Mootha VK, DiMauro S et al (2005) Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation. Neurology 64:539–541

    Article  PubMed  CAS  Google Scholar 

  • Quinzii C, Naini A, Salviati L, Trevisson E, Navas P, DiMauro S et al (2006) A mutation in para-Hydoxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency. Am J Hum Genet 78:345–349

    Article  PubMed  CAS  Google Scholar 

  • Ravera S, Panfoli I, Calzia D, Aluigi MG, Bianchini P, Diaspro A et al (2009) Evidence for aerobic ATP synthesis in isolated myelin vesicles. Int J Biochem Cell Biol 41:1581–1591

    Article  PubMed  CAS  Google Scholar 

  • Roesch K, Curran SP, Tranebjaerg L, Koehler CM (2002) Human deafness dystonia syndrome is caused by a defect in assembly of the DDP1/TIMM8a-TIMM13 complex. Hum Mol Genet 11:477–486

    Article  PubMed  CAS  Google Scholar 

  • Rotig A, Appelkvist E-L, Geromel V, Chretien D, Kadhom N, Edery P et al (2000) Quinone-responsive multiple respiratory-chain dysfunction due to widespread coenzyme Q10 deficiency. Lancet 356:391–395

    Article  PubMed  CAS  Google Scholar 

  • Rotig A, Poulton J (2009) Genetic causes of mitochondrial DNA depletion in humans. Biochim Biophys Acta 1792:1103–1108

    PubMed  Google Scholar 

  • Rowland LP (1994) Mitochondrial encephalomyopathies: lumping, splitting, and melding. In: Schapira AHV, DiMauro S (eds) Mitochondrial disorders in neurology. Butterworth-Heinemann, Oxford, pp 116–129

    Google Scholar 

  • Saada A, Shaag A, Mandel H, Nevo Y, Eriksson S, Elpeleg O (2001) Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat Genet 29:342–344

    Article  PubMed  CAS  Google Scholar 

  • Sacconi S, Salviati L, Nishigaki Y, Walker WF, Hernandez-Rosa E, Trevisson E et al (2008) A functionally dominant mitochondrial DNA mutation. Hum Mol Genet 17:1814–1820

    Article  PubMed  CAS  Google Scholar 

  • Salviati L, Sacconi S, Murer L, Zacchello G, Franceschini L, Laverda AM et al (2005) Infantile encephalomyopathy and nephropathy with CoQ10 deficiency: a CoQ10-responsive condition. Neurology 65:606–608

    Article  PubMed  CAS  Google Scholar 

  • Schaefer AM, Taylor RW, Turnbull DM, Chinnery PF (2004) The epidemiology of mitochondrial disorders-past, present and future. Biochim Biophys Acta 1659:115–120

    Article  PubMed  CAS  Google Scholar 

  • Schaefer AM, McFarland R, Blakely E, Langping H, Whittaker RG, Taylor RW et al (2008) Prevalence of mitochondrial DNA disease in adults. Ann Neurol 63(1):35–39

    Google Scholar 

  • Scheffler IE (1986) Biochemical genetics of respiration-deficient mutants of animal cells. In: Morgan MJ (ed) Carbohydrate metabolism in cultured cells. Plenum, London, pp 77–109

    Google Scholar 

  • Scheper GC, Klok VD, van Andel RJ, van Berkel CGM, Sissler M, Smet J et al (2007) Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Nat Genet 39:534–538

    Article  PubMed  CAS  Google Scholar 

  • Schlame M, Ren M (2006) Barth syndrome, a human disorder of cardiolipin metabolism. FEBS Lett 580:5450–5455

    Article  PubMed  CAS  Google Scholar 

  • Schlame M, Towbin JA, Heerdt PM, Jehle R, DiMauro S, Blanck TJJ (2002) Deficiency of tetralinoleoyl-cardiolipin in Barth syndrome. Ann Neurol 51:634–637

    Article  PubMed  CAS  Google Scholar 

  • Schwartz F, Vissing J (2004) No evidence of paternal inheritance of mtDNA in patients with sporadic mtDNA mutations. J Neurol Sci 218:99–101

    Article  PubMed  CAS  Google Scholar 

  • Schwartz M, Vissing J (2002) Paternal inheritance of mitohondrial DNA. New Engl J Med 347:576–580

    Article  PubMed  Google Scholar 

  • Servidei S (2001) Mitochondrial encephalomyopathies: gene mutation. Neuromuscul Disord 14:107–116

    Google Scholar 

  • Shankar SP, Fingert JH, Carelli V, Valentino ML, King TM, Daiger SP et al (2008) Evidence for a novel X-linked modifier locus for Leber hereditary optic neuropathy. Opthal Genet 29:17–24

    Article  CAS  Google Scholar 

  • Shapira Y, Harel S, Russell A (1977) Mitochondrial encephalomyopathies: a group of neuromuscular disorders with defects in oxidative metabolism. Isr J Med Sci 13:161–164

    PubMed  CAS  Google Scholar 

  • Shoffner JM, Lott MT, Lezza A, Seibel P, Ballinger SW, Wallace DC (1990) Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNALys mutation. Cell 61:931–937

    Article  PubMed  CAS  Google Scholar 

  • Shy GM, Gonatas NK (1964) Human myopathy with giant abnormal mitochondria. Science 145:493–496

    Article  PubMed  CAS  Google Scholar 

  • Shy GM, Gonatas NK (1966) Two childhood myopathies with abnormal mitochondria: I. Megaconial myopathy; II. Pleoconial myopathy. Brain 89:133–158

    Article  PubMed  CAS  Google Scholar 

  • Skladal D, Halliday J, Thorburn DR (2003) Minimum birth prevalence of mitochondrial respiratory chain disorders in children. Brain 126:1905–1912

    Article  PubMed  Google Scholar 

  • Smeitink J, van den Heuvel L (1999) Protein biosynthesis ′99: human mitochondrial complex I in health and disease. Am J Hum Genet 64:1505–1510

    Article  PubMed  CAS  Google Scholar 

  • Smeitink JAM, Elpeleg O, Antonicka H, Diepstra H, Saada A, Smits P et al (2006) Distinct clinical phenotypes associated with a mutation in the mitochondrial translation elongation factor EFTs. Am J Hum Genet 79:869–877

    Article  PubMed  CAS  Google Scholar 

  • Sobreira C, Hirano M, Shanske S, Keller RK, Haller RG, Davidson E et al (1997) Mitochondrial encephalomyopathy with coenzyme Q10 deficiency. Neurology 48:1238–1243

    PubMed  CAS  Google Scholar 

  • Spelbrink JN, Li FY, Tiranti V, Nikali K, Yuan QP, Tariq M et al (2001) Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria. Nat Genet 28:200–201

    Article  Google Scholar 

  • Sperl W, Jesina P, Zeman J, Mayr JA, DeMeirleir L, VanCoster R et al (2006) Deficiency of mitochondrial ATP synthase of nuclear origin. Neuromuscul Disord 16:821–829

    Article  PubMed  CAS  Google Scholar 

  • Spinazzola A, Marti R, Nishino I, Andreu AL, Naini A, Tadesse S et al (2002) Altered thymidine metabolism due to defects of thymidine phosphorylase. J Biol Chem 277:4128–4132

    Article  PubMed  CAS  Google Scholar 

  • Spinazzola A, Zeviani M (2005) Disorders of nuclear-mitochondrial intergenomic signaling. Gene 354:162–168

    Article  PubMed  CAS  Google Scholar 

  • Spinazzola A, Invernizzi F, Carrara F, Lamantea E, Donati A, Dirocco M, Giordano I et al (2009) Clinical and molecular features of mitochondrial DNA depletion syndromes. J Inherit Metab Dis 32:143–158

    Article  PubMed  CAS  Google Scholar 

  • Spiro AJ, Moore CL, Prineas JW, Strasberg PM, Rapin I (1970) A cytochrome-related inherited disorder of the nervous system and muscle. Arch Neurol 23:103–112

    PubMed  CAS  Google Scholar 

  • Sue CM, Tanji K, Hadjigeorgiou G, Andreu AL, Nishino I, Krishna S et al (1999) Maternally inherited hearing loss in a large kindred with a novel mutation in the mitochondrial DNA tRNASer(UCN) gene. Neurology 52:1905–1908

    PubMed  CAS  Google Scholar 

  • Takakubo F, Cartwright P, Hoogenraad N, Thorburn DR, Collins F, Lithgow T et al (1995) An amino acid substitution in the pyruvate dehydrogenase E1a gene, affecting mitochondrial import of the precursor protein. Am J Hum Genet 57:772–780

    PubMed  CAS  Google Scholar 

  • Tanji K, Bonilla E (2001) Optical imaging techniques (histochemical, immunohistochemical, and in situ hybridization staining methods) to visualize mitochondria. Meth Cell Biol 65:311–332

    Article  CAS  Google Scholar 

  • Tatuch Y, Christodoulou J, Feigenbaum A, Clarke J, Wherret J, Smith C et al (1992) Heteroplasmic mtDNA mutation (T > G) at 8993 can cause Leigh disease when the percentage of abnormal mtDNA is high. Am J Hum Genet 50:852–858

    PubMed  CAS  Google Scholar 

  • Taylor RW, Giordano C, Davidson MM, d’Amati G, Bain H, Hayes CM et al (2003a) A homoplasmic mitochondrial transfer ribonucleic acid mutation as a cause of maternally inherited cardiomyopathy. J Am Coll Cardiol 41:1786–1796

    Article  CAS  Google Scholar 

  • Taylor RW, McDonnell MT, Blakely EL, Chinnery PF, Taylor GA, Howell N et al (2003b) Genotypes from patients indicate no paternal mitochondrial contribution. Ann Neurol 54:521–524

    Article  PubMed  CAS  Google Scholar 

  • Tiranti V, Hoertnagel K, Carrozzo R, Galimberti C, Munaro M, Granatiero M et al (1998) Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency. Am J Hum Genet 63:1609–1621

    Article  PubMed  CAS  Google Scholar 

  • Tiranti V, D'Adamo P, Briem E, Ferrari G, Mineri R, Lamantea E et al (2004) Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein. Am J Hum Genet 74:239–252

    Article  PubMed  CAS  Google Scholar 

  • Tiranti V, Briem E, Lamantea E, Mineri R, Papaleo E, De Gioia L et al (2006) ETHE1 mutations are specific to ethylmalonic encephalopathy. J Med Genet 43:340–346

    Article  PubMed  CAS  Google Scholar 

  • Tiranti V, Visconti C, Hildebrandt T, Di Meo I, Mineri R, Tiveron C et al (2009) Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy. Nat Med 15:200–205

    Article  PubMed  CAS  Google Scholar 

  • Tzoulis C, Engelsen BA, Telstad W, Aasly J, Zeviani M, Winterthun S et al (2006) The spectrum of clinical disease caused by the A467T and W748S POLG mutations: a study of 26 cases. Brain 129:1685–1692

    Article  PubMed  Google Scholar 

  • Valente L, Tiranti V, Marsano RM, Malfatti E, Fernandez-Vizarra E, Donnini C et al (2007) Infantile encephalopathy and defective mitochondrial DNA translation in patients with mutations of mitochondrial elongation factors EGF1 and EFTu. Am J Hum Genet 80:44–58

    Article  PubMed  CAS  Google Scholar 

  • Valnot I, Osmond S, Gigarel N, Mehaye B, Amiel J, Cormier-Daire V et al (2000a) Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy. Am J Hum Genet 67:1104–1109

    PubMed  CAS  Google Scholar 

  • Valnot I, von Kleist-Retzow J-C, Barrientos A, Gorbatyuk M, Taanman J-W, Mehaye B et al (2000b) A mutation in the human heme-A:farnesyltransferase gene (COX 10) causes cytochrome c oxidase deficiency. Hum Mol Genet 9:1245–1249

    Article  PubMed  CAS  Google Scholar 

  • Van Goethem G, Dermaut B, Lofgren A, Martin J-J, Van Broeckhoven C (2001) Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nat Genet 28:211–212

    Article  PubMed  CAS  Google Scholar 

  • Van Maldergem L, Trijbels F, DiMauro S, Sindelar PJ, Musumeci O, Janssen A et al (2002) Coenzyme Q-responsive Leigh's encephalopathy in two sisters. Ann Neurol 52:750–754

    Article  PubMed  CAS  Google Scholar 

  • Visapaa I, FEellman V, Vesa J, Dasvarma A, Hutton JL, Kumar V et al (2002) GRACILE syndrome, a lethal metabolic disorder with iron overload, is caused by a point mutation in BCS1L. Am J Hum Genet 71:863–876

    Article  PubMed  Google Scholar 

  • Vreken P, Valianpour F, Nijtmans LG, Grivell LA, Plecko B, Wanders RJ et al (2000) Defective remodeling of cardiolipin and phosphatidylglycerol in Barth syndrome. Biochem Biophys Res Comm 279:378–382

    Article  PubMed  CAS  Google Scholar 

  • Wai T, Teoli D, Shoubridge EA (2010) The mitochondrial DNA genetic bottleneck results from replication of a subpopulation of genomes. Nat Genet 40:1484–1488

    Article  CAS  Google Scholar 

  • Wallace DC (2005) The mitochondrial genome in human adaptive radiation and disease: on the road to therapeutics and performance enhancement. Gene 354:169–180

    Article  PubMed  CAS  Google Scholar 

  • Wallace DC, Singh G, Lott MT, Hodge JA, Schurr TG, Lezza A et al (1988) Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science 242:1427–1430

    Article  PubMed  CAS  Google Scholar 

  • Willems JL, Monnens L, Trijbels J, Veerkamp JH, Meyer A, van Dam K et al (1977) Leigh's encephalomyelopathy in a patient with cytochrome c oxidase deficiency in muscle tissue. Pediatrics 60:850–857

    PubMed  CAS  Google Scholar 

  • Yu Y, Malhotra A, Ren M, Schlame M (2006) The enzymatic function of tafazzin. J Biol Chem 281:39217–39224

    Article  CAS  Google Scholar 

  • Zanna C, Ghelli A, Porcelli AM, Karbowski M, Youle RJ, Schimpf S et al (2008) OPA1 mutations associated with dominant optic atrophy impair oxidative phosphorylation and mitochondrial fusion. Brain 131:352–367

    Article  PubMed  Google Scholar 

  • Zeviani M, Moraes CT, DiMauro S (1988) Deletions of mitochondrial DNA in Kearns-Sayre syndrome. Neurology 38:1339–1346

    PubMed  CAS  Google Scholar 

  • Zeviani M, Servidei S, Gellera C, Bertini E, DiMauro S, DiDonato S (1989) An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D-loop region. Nature 339:309–311

    Article  PubMed  CAS  Google Scholar 

  • Zhu Z, Yao J, Johns T, Fu K, De Bie I, Macmillan C et al (1998) SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome. Nat Genet 20:337–343

    Article  PubMed  CAS  Google Scholar 

  • Zuchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL et al (2004) Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet 36:449–451

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

I thank my colleagues and friends Eric Schon and Michio Hirano for reviewing the manuscript.

This work was supported by NIH grant HD032062 and by the Marriott Mitochondrial Clinical Research Fund (MMCRF).

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  1. Department of Neurology, Columbia University Medical Center, Room 4-424B College of Physicians & Surgeons, 630 West 168th Street, New York, NY, 10032, USA

    Salvatore DiMauro

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Correspondence to Salvatore DiMauro.

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Communicated by: Jan Smeitink

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DiMauro, S. A history of mitochondrial diseases. J Inherit Metab Dis 34, 261–276 (2011). https://doi.org/10.1007/s10545-010-9082-x

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