1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Vision Science
  4. Volume 1, 2015
  5. Article

Annual Review of Vision Science

Volume 1, 2015

Mitochondrial Genetics and Optic Neuropathy

Abstract

Mitochondrial dysfunction underlies many human disorders, including those that affect the visual system. The retinal ganglion cells, whose axons form the optic nerve, are often damaged by mitochondrial-related diseases which result in blindness. Both mitochondrial DNA (mtDNA) and nuclear gene mutations impacting many different mitochondrial processes can result in optic nerve disease. Of particular importance are mutations that impair mitochondrial network dynamics (fusion and fission), oxidative phosphorylation (OXPHOS), and formation of iron–sulfur complexes. Current genetic knowledge can inform genetic counseling and suggest strategies for novel gene-based therapies. Identifying new optic neuropathy–causing genes and defining the role of current and novel genes in disease will be important steps toward the development of effective and potentially neuroprotective therapies.

Keyword(s): iron-sulfur complexes, mitochondria, mitochondrial network, optic neuropathy, oxidative phosphorylation, papillomacular bundle, visual field
Loading

Article metrics loading...

/content/journals/10.1146/annurev-vision-082114-035651
2015-11-24
2024-05-06
Loading full text...

Full text loading...

/deliver/fulltext/vision/1/1/annurev-vision-082114-035651.html?itemId=/content/journals/10.1146/annurev-vision-082114-035651&mimeType=html&fmt=ahah

Literature Cited

  1. Abu-Amero KK, Morales J, Bosley TM, Mohamed GH, Cabrera VM. 2008. The role of mitochondrial haplogroups in glaucoma: a study in an Arab population. Mol. Vis. 14:518–22 [Google Scholar]
  2. Akabane S, Ueda T, Nierhaus KH, Takeuchi N. 2014. Ribosome rescue and translation termination at non-standard stop codons by ICT1 in mammalian mitochondria. PLOS Genet. 10:9e1004616 [Google Scholar]
  3. Alavi MV, Fuhrmann N. 2013. Dominant optic atrophy, OPA1, and mitochondrial quality control: understanding mitochondrial network dynamics. Mol. Neurodegener. 8:32 [Google Scholar]
  4. Allen KF, Gaier ED, Wiggs JL. 2015. Genetics of primary inherited disorders of the optic nerve: clinical applications. Cold Spring Harb. Perspect. Med. 5:a017277 [Google Scholar]
  5. Amati-Bonneau P, Milea D, Bonneau D, Chevrollier A, Ferré M. et al. 2009. OPA1-associated disorders: phenotypes and pathophysiology. Int. J. Biochem. Cell Biol. 41:101855–65 [Google Scholar]
  6. Amati-Bonneau P, Valentino ML, Reynier P, Gallardo ME, Bornstein B. et al. 2008. OPA1 mutations induce mitochondrial DNA instability and optic atrophy ‘plus’ phenotypes. Brain 131:338–51 [Google Scholar]
  7. Angebault C, Gueguen N, Desquiret-Dumas V, Chevrollier A, Guillet V. et al. 2011. Idebenone increases mitochondrial complex I activity in fibroblasts from LHON patients while producing contradictory effects on respiration. BMC Res. Notes 4:557 [Google Scholar]
  8. Anikster Y, Kleta R, Shaag A, Gahl WA, Elpeleg O. 2001. Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi jews. Am. J. Hum. Genet. 69:61218–24 [Google Scholar]
  9. Antonicka H, Østergaard E, Sasarman F, Weraarpachai W, Wibrand F. et al. 2010. Mutations in C12orf65 in patients with encephalomyopathy and a mitochondrial translation defect. Am. J. Hum. Genet. 87:1115–22 [Google Scholar]
  10. Aung T, Rezaie T, Okada K, Viswanathan AC, Child AH. et al. 2005. Clinical features and course of patients with glaucoma with the E50K mutation in the optineurin gene. Investig. Ophthalmol. Vis. Sci. 46:82816–22 [Google Scholar]
  11. Badura-Stronka M, Wawrocka A, Zawieja K, Silska S, Krawczyński MR. 2013. Severe manifestation of Leber's hereditary optic neuropathy due to 11778G>A mtDNA mutation in a female with hypoestrogenism due to Perrault syndrome. Mitochondrion 13:6831–34 [Google Scholar]
  12. Barbet F, Gerber S, Hakiki S, Perrault I, Hanein S. et al. 2003. A first locus for isolated autosomal recessive optic atrophy (ROA1) maps to chromosome 8q. Eur. J. Hum. Genet. 11:12966–71 [Google Scholar]
  13. Barbet F, Hakiki S, Orssaud C, Gerber S, Perrault I. et al. 2005. A third locus for dominant optic atrophy on chromosome 22q. J. Med. Genet. 42:1e1 [Google Scholar]
  14. Barboni P, Savini G, Cascavilla ML, Caporali L, Milesi J. et al. 2014. Early macular retinal ganglion cell loss in dominant optic atrophy: genotype-phenotype correlation. Am. J. Ophthalmol. 158:3628–36.e3 [Google Scholar]
  15. Baris O, Delettre C, Amati-Bonneau P, Surget M-O, Charlin J-F. et al. 2003. Fourteen novel OPA1 mutations in autosomal dominant optic atrophy including two de novo mutations in sporadic optic atrophy. Hum. Mutat. 21:6656 [Google Scholar]
  16. Barron MJ, Griffiths P, Turnbull DM, Bates D, Nichols P. 2004. The distributions of mitochondria and sodium channels reflect the specific energy requirements and conduction properties of the human optic nerve head. Br. J. Ophthalmol. 88:2286–90 [Google Scholar]
  17. Bénit P, Slama A, Cartault F, Giurgea I, Chretien D. et al. 2004. Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome. J. Med. Genet. 41:114–17 [Google Scholar]
  18. Binder J, Hofmann S, Kreisel S, Wöhrle JC, Bäzner H. et al. 2003. Clinical and molecular findings in a patient with a novel mutation in the deafness–dystonia peptide (DDP1) gene. Brain 126:1814–20 [Google Scholar]
  19. Biousse V, Brown MD, Newman NJ, Allen JC, Rosenfeld J. et al. 1997. De novo 14484 mitochondrial DNA mutation in monozygotic twins discordant for Leber's hereditary optic neuropathy. Neurology 49:41136–38 [Google Scholar]
  20. Bonifert T, Karle KN, Tonagel F, Batra M, Wilhelm C. et al. 2014. Pure and syndromic optic atrophy explained by deep intronic OPA1 mutations and an intralocus modifier. Brain 137:2164–77 [Google Scholar]
  21. Bridwell-Rabb J, Winn AM, Barondeau DP. 2011. Structure-function analysis of Friedreich's ataxia mutants reveals determinants of frataxin binding and activation of the Fe-S assembly complex. Biochemistry 50:337265–74 [Google Scholar]
  22. Buono LM, Foroozan R, Sergott RC, Savino PJ. 2002. Is normal tension glaucoma actually an unrecognized hereditary optic neuropathy? New evidence from genetic analysis. Curr. Opin. Ophthalmol. 13:6362–70 [Google Scholar]
  23. Burté F, Carelli V, Chinnery PF, Yu-Wai-Man P. 2015. Disturbed mitochondrial dynamics and neurodegenerative disorders. Nat. Rev. Neurol. 11:111–24 [Google Scholar]
  24. Calvo SE, Mootha VK. 2010. The mitochondrial proteome and human disease. Annu. Rev. Genomics Hum. Genet. 11:25–44 [Google Scholar]
  25. Carelli V, La Morgia C, Valentino ML, Barboni P, Ross-Cisneros FN, Sadun AA. 2009. Retinal ganglion cell neurodegeneration in mitochondrial inherited disorders. Biochim. Biophys. Acta 1787:5518–28 [Google Scholar]
  26. Carelli V, La Morgia C, Valentino ML, Rizzo G, Carbonelli M. et al. 2011a. Idebenone treatment in Leber's hereditary optic neuropathy. Brain 134:e188 [Google Scholar]
  27. Carelli V, Schimpf S, Fuhrmann N, Valentino ML, Zanna C. et al. 2011b. A clinically complex form of dominant optic atrophy (OPA8) maps on chromosome 16. Hum. Mol. Genet. 20:101893–905 [Google Scholar]
  28. Casari G, De Fusco M, Ciarmatori S, Zeviani M, Mora M. et al. 1998. Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell 93:6973–83 [Google Scholar]
  29. Chalmers RM, Davis MB, Sweeney MG, Wood NW, Harding AE. 1996. Evidence against an X-linked visual loss susceptibility locus in Leber hereditary optic neuropathy. Am. J. Hum. Genet. 59:1103–8 [Google Scholar]
  30. Chang CR, Manlandro CM, Arnoult D, Stadler J, Posey AE. et al. 2010. A lethal de novo mutation in the middle domain of the dynamin-related GTPase Drp1 impairs higher order assembly and mitochondrial division. J. Biol. Chem. 285:4232494–503 [Google Scholar]
  31. Chen H, Chan DC. Critical dependence of neurons on mitochondrial dynamics; 2006. Curr. Opin. Cell Biol. 18:453–59 [Google Scholar]
  32. Chen L, Gong Q, Stice JP, Knowlton AA. 2009. Mitochondrial OPA1, apoptosis, and heart failure. Cardiovasc. Res. 84:191–99 [Google Scholar]
  33. Chen Y-F, Kao C-H, Chen Y-T, Wang C-H, Wu C-Y. et al. 2009. Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes Dev. 23:101183–94 [Google Scholar]
  34. Chinnery PF, Andrews RM, Turnbull DM, Howell N. 2001. Leber hereditary optic neuropathy: Does heteroplasmy influence the inheritance and expression of the G11778A mitochondrial DNA mutation?. Am. J. Med. Genet. 98:235–43 [Google Scholar]
  35. Chung KW, Kim SB, Park KD, Choi KG, Lee JH. et al. 2006. Early onset severe and late-onset mild Charcot–Marie–Tooth disease with mitofusin 2 (MFN2) mutations. Brain 129:2103–18 [Google Scholar]
  36. Cirulli ET, Lasseigne BN, Petrovski S, Sapp PC, Dion PA. et al. 2015. Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science 347:1436–41 [Google Scholar]
  37. Cogliati S, Frezza C, Soriano ME, Varanita T, Quintana-Cabrera R. et al. 2013. Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency. Cell 155:1160–71 [Google Scholar]
  38. Cohn AC, Toomes C, Hewitt AW, Kearns LS, Inglehearn CF. et al. 2008. The natural history of OPA1-related autosomal dominant optic atrophy. Br. J. Ophthalmol. 92:101333–36 [Google Scholar]
  39. Cohn AC, Toomes C, Potter C, Towns KV, Hewitt AW. et al. 2007. Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations. Am. J. Ophthalmol. 143:4656–62 [Google Scholar]
  40. Copeland WC. 2014. Defects of mitochondrial DNA replication. J. Child Neurol. 29:91216–24 [Google Scholar]
  41. Consugar MB, Navarro-Gomez D, Place EM, Bujakowska KM, Sousa ME. et al. 2015. Panel-based genetic diagnostic testing for inherited eye diseases is highly accurate and reproducible, and more sensitive for variant detection, than exome sequencing. Genet. Med. 17:253–61 [Google Scholar]
  42. Crosby AH, Patel H, Chioza BA, Proukakis C, Gurtz K. et al. 2010. Defective mitochondrial mRNA maturation is associated with spastic ataxia. Am. J. Hum. Genet. 87:5655–60 [Google Scholar]
  43. Dames S, Eilbeck K, Mao R. 2015. A high-throughput next-generation sequencing assay for the mitochondrial genome. Methods Mol. Biol. 1264:77–88 [Google Scholar]
  44. Davies VJ, Powell KA, White KE, Yip W, Hogan V. et al. 2008. A missense mutation in the murine Opa3 gene models human Costeff syndrome. Brain 131:368–80 [Google Scholar]
  45. Davis CH, Kim K-Y, Bushong EA, Mills EA, Boassa D. et al. 2014. Transcellular degradation of axonal mitochondria. PNAS 111:269633–38 [Google Scholar]
  46. Davis CH, Marsh-Armstrong N. 2014. Discovery and implications of transcellular mitophagy. Autophagy 10:122383–84 [Google Scholar]
  47. de Heredia ML, Clèries R, Nunes V. 2013. Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype. Genet. Med. 15:7497–506 [Google Scholar]
  48. Delettre C, Lenaers G, Griffoin JM, Gigarel N, Lorenzo C. et al. 2000. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat. Genet. 26:2207–10 [Google Scholar]
  49. De Vriese AS, Coster RV, Smet J, Seneca S, Lovering A. et al. 2006. Linezolid-induced inhibition of mitochondrial protein synthesis. Clin. Infect. Dis. 42:81111–17 [Google Scholar]
  50. Désir J, Coppieters F, Van Regemorter N, De Baere E, Abramowicz M, Cordonnier M. 2012. TMEM126A mutation in a Moroccan family with autosomal recessive optic atrophy. Mol. Vis. 18:1849–57 [Google Scholar]
  51. Dimitriadis K, Leonhardt M, Yu-Wai-Man P, Kirkman MA, Korsten A. et al. 2014. Leber's hereditary optic neuropathy with late disease onset: clinical and molecular characteristics of 20 patients. Orphanet J. Rare Dis. 9:158 [Google Scholar]
  52. Elgass K, Pakay J, Ryan MT, Palmer CS. 2013. Recent advances into the understanding of mitochondrial fission. Biochim. Biophys. Acta 1833:1150–61 [Google Scholar]
  53. Eura Y, Ishihara N, Yokota S, Mihara K. 2003. Two mitofusin proteins, mammalian homologues of FZO, with distinct functions are both required for mitochondrial fusion. J. Biochem. 134:3333–44 [Google Scholar]
  54. Federico A, Cardaioli E, Da Pozzo P, Formichi P, Gallus GN, Radi E. 2012. Mitochondria, oxidative stress and neurodegeneration. J. Neurol. Sci. 322:254–62 [Google Scholar]
  55. Ferré M, Amati-Bonneau P, Tourmen Y, Malthièry Y, Reynier P. 2005. eOPA1: an online database for OPA1 mutations. Hum. Mutat. 25:5423–28 [Google Scholar]
  56. Ferré M, Bonneau D, Milea D, Chevrollier A, Verny C. et al. 2009. Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations. Hum. Mutat. 30:7E692–705 [Google Scholar]
  57. Ferré M, Caignard A, Milea D, Leruez S, Cassereau J. et al. 2015. Improved locus-specific database for OPA1 mutations allows inclusion of advanced clinical data. Hum. Mutat. 36:120–25 [Google Scholar]
  58. Fingert JH, Robin AL, Stone JL, Roos BR, Davis LK. et al. 2011. Copy number variations on chromosome 12q14 in patients with normal tension glaucoma. Hum. Mol. Genet. 20:122482–94 [Google Scholar]
  59. Fortuna F, Barboni P, Liguori R, Valentino ML, Savini G. et al. 2009. Visual system involvement in patients with Friedreich's ataxia. Brain 132:116–23 [Google Scholar]
  60. Frank S, Gaume B, Bergmann-Leitner ES, Leitner WW, Robert EG. et al. 2001. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev. Cell 1:4515–25 [Google Scholar]
  61. Frezza C, Cipolat S, Martins de Brito O, Micaroni M, Beznoussenko GV. et al. 2006. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell 126:177–89 [Google Scholar]
  62. Galluzzi L, Kepp O, Kroemer G. 2011. Autophagy and innate immunity ally against bacterial invasion. EMBO J. 30:163213–14 [Google Scholar]
  63. Gegg ME, Cooper JM, Chau K-Y, Rojo M, Schapira AH, Taanman JW. 2010. Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum. Mol. Genet. 19:244861–70 [Google Scholar]
  64. Gibson SB. 2013. Investigating the role of reactive oxygen species in regulating autophagy. Methods Enzymol. 528:217–35 [Google Scholar]
  65. Giordano C, Iommarini L, Giordano L, Maresca A, Pisano A. et al. 2014. Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy. Brain 137:335–53 [Google Scholar]
  66. Gomes CM, Santos R. 2013. Neurodegeneration in Friedreich's ataxia: from defective frataxin to oxidative stress. Oxid. Med. Cell Longev. 2013:487534 [Google Scholar]
  67. Griffin EE, Detmer SA, Chan DC. 2006. Molecular mechanism of mitochondrial membrane fusion. Biochim. Biophys. Acta 1763:482–89 [Google Scholar]
  68. Ha AD, Parratt KL, Rendtorff ND, Lodahl M, Ng K. et al. 2012. The phenotypic spectrum of dystonia in Mohr–Tranebjaerg syndrome. Mov. Disord. 27:81034–40 [Google Scholar]
  69. Haelterman NA, Yoon WH, Sandoval H, Jaiswal M, Shulman JM, Bellen HJ. 2014. A mitocentric view of Parkinson's disease. Annu. Rev. Neurosci. 37:137–59 [Google Scholar]
  70. Han J, Lee Y-M, Kim SM, Han SY, Lee JB, Han S-H. 2014. Ophthalmological manifestations in patients with Leigh syndrome. Br. J. Ophthalmol. 99:528–35 [Google Scholar]
  71. Han J, Thompson-Lowrey AJ, Reiss A, Mayorov V, Jia H. et al. 2006. OPA1 mutations and mitochondrial DNA haplotypes in autosomal dominant optic atrophy. Genet. Med. 8:4217–25 [Google Scholar]
  72. Hanein S, Garcia M, Fares-Taie L, Serre V, De Keyzer Y. et al. 2013. TMEM126A is a mitochondrial located mRNA (MLR) protein of the mitochondrial inner membrane. Biochim. Biophys. Acta 1830:63719–33 [Google Scholar]
  73. Hanein S, Perrault I, Roche O, Gerber S, Khadom N. et al. 2009. TMEM126A, encoding a mitochondrial protein, is mutated in autosomal-recessive nonsyndromic optic atrophy. Am. J. Hum. Genet. 84:4493–98 [Google Scholar]
  74. Harding AE, Sweeney MG, Govan GG, Riordan-Eva P. 1995. Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation. Am. J. Hum. Genet. 57:177–86 [Google Scholar]
  75. Harrington DO, Drake MV. 1990. The Visual Fields: Textbook and Atlas of Clinical Perimetry St. Louis: CV Mosby
  76. Heidary G, Calderwood L, Cox GF, Robson CD, Teot LA. et al. 2014. Optic atrophy and a Leigh-like syndrome due to mutations in the c12orf65 gene: report of a novel mutation and review of the literature. J. Neuroophthalmol. 34:139–43 [Google Scholar]
  77. Heitz FD, Erb M, Anklin C, Robay D, Pernet V, Gueven N. 2012. Idebenone protects against retinal damage and loss of vision in a mouse model of Leber's hereditary optic neuropathy. PLOS ONE 7:9e45182 [Google Scholar]
  78. Hoekel J, Chisholm SA, Al-Lozi A, Hershey T, Tychsen L. (Wash. Univ. Wolfram Study Group) 2014. Ophthalmologic correlates of disease severity in children and adolescents with Wolfram syndrome. J. AAPOS 18:5461–465.e1 [Google Scholar]
  79. Horga A, Pitceathly RD, Blake JC, Woodward CE, Zapater P. et al. 2014. Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia. Brain 137:3200–12 [Google Scholar]
  80. Howell N, Herrnstadt C, Shults C, Mackey DA. 2003. Low penetrance of the 14484 LHON mutation when it arises in a non-haplogroup J mtDNA background. Am. J. Med. Genet. A 119A:2147–51 [Google Scholar]
  81. Hudson G, Amati-Bonneau P, Blakely EL, Stewart JD, He L. 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 131:329–37 [Google Scholar]
  82. Hudson G, Carelli V, Spruijt L, Gerards M, Mowbray C. et al. 2007. Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA–haplogroup background. Am. J. Hum. Genet. 81:2228–33 [Google Scholar]
  83. Hudson G, Gomez-Duran A, Wilson IJ, Chinnery PF. 2014. Recent mitochondrial DNA mutations increase the risk of developing common late-onset human diseases. PLOS Genet. 10:5e1004369 [Google Scholar]
  84. Huoponen K, Puomila A, Savontaus ML, Mustonen E, Kronqvist E, Nikoskelainen E. 2002. Genetic counseling in Leber hereditary optic neuropathy (LHON). Acta Ophthalmol. Scand. 80:138–43 [Google Scholar]
  85. Hwang J-M, Kim J, Park SS. 2003. Leber's hereditary optic neuropathy mutations in ethambutol-induced optic neuropathy. J. Neurol. 250:187–89 [Google Scholar]
  86. Ito Y, Nakamura M, Yamakoshi T, Lin J, Yatsuya H, Terasaki H. 2007. Reduction of inner retinal thickness in patients with autosomal dominant optic atrophy associated with OPA1 mutations. Investig. Ophthalmol. Vis. Sci. 48:94079–86 [Google Scholar]
  87. Jacobi FK, Leo-Kottler B, Mittelviefhaus K, Zrenner E, Meyer J. et al. 2001. Segregation patterns and heteroplasmy prevalence in Leber's hereditary optic neuropathy. Investig. Ophthalmol. Vis. Sci. 42:61208–14 [Google Scholar]
  88. Janssen RJ, Nijtmans LG, van den Heuvel LP, Smeitink JA. 2006. Mitochondrial complex I: structure, function and pathology. J. Inherit. Metab. Dis. 29:4499–515 [Google Scholar]
  89. Javaheri M, Khurana RN, O’Hearn TM, Lai MM, Sadun AA. 2007. Linezolid-induced optic neuropathy: a mitochondrial disorder?. Br. J. Ophthalmol. 91:1111–15 [Google Scholar]
  90. Jeoung JW, Seong M-W, Park SS, Kim DM, Kim SH, Park KH. 2014. Mitochondrial DNA variant discovery in normal-tension glaucoma patients by next-generation sequencing. Investig. Ophthalmol. Vis. Sci. 55:2986–92 [Google Scholar]
  91. Katz BJ, Zhao Y, Warner JE, Tong Z, Yang Z, Zhang K. 2006. A family with X-linked optic atrophy linked to the OPA2 locus Xp11.4-Xp11.2. Am. J. Med. Genet. A 140:202207–11 [Google Scholar]
  92. Kembro JM, Aon MA, Winslow RL, O’Rourke B, Cortassa S. 2013. Integrating mitochondrial energetics, redox and ROS metabolic networks: a two-compartment model. Biophys. J. 104:2332–43 [Google Scholar]
  93. Kerrison JB, Arnould VJ, Ferraz Sallum JM, Vagefi MR, Barmada MM. et al. 1999. Genetic heterogeneity of dominant optic atrophy, Kjer type: identification of a second locus on chromosome 18q12.2–12.3. Arch. Ophthalmol. 117:6805–10 [Google Scholar]
  94. Kersten HM, Roxburgh RH, Danesh-Meyer HV. 2014. Ophthalmic manifestations of inherited neurodegenerative disorders. Nat. Rev. Neurol. 10:6349–62 [Google Scholar]
  95. Kirkman MA, Yu-Wai-Man P, Korsten A, Leonhardt M, Dimitriadis K. et al. 2009. Gene–environment interactions in Leber hereditary optic neuropathy. Brain 132:2317–26 [Google Scholar]
  96. Kitani T, Kami D, Kawasaki T, Nakata M, Matoba S, Gojo S. 2014. Direct human mitochondrial transfer: a novel concept based on the endosymbiotic theory. Transplant. Proc. 46:41233–36 [Google Scholar]
  97. Klebe S, Depienne C, Gerber S, Challe G, Anheim M. et al. 2012. Spastic paraplegia gene 7 in patients with spasticity and/or optic neuropathy. Brain 135:2980–93 [Google Scholar]
  98. Kline LB. 1996. Optic Nerve Disorders. San Francisco: Am. Acad. Ophthalmol.
  99. Klopstock T, Metz G, Yu-Wai-Man P, Büchner B, Gallenmüller C. et al. 2013. Persistence of the treatment effect of idebenone in Leber's hereditary optic neuropathy. Brain 136:e230 [Google Scholar]
  100. Klopstock T, Yu-Wai-Man P, Dimitriadis K, Rouleau J, Heck S. et al. 2011. A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy. Brain 134:2677–86 [Google Scholar]
  101. Koilkonda R, Yu H, Talla V, Porciatti V, Feuer WJ. et al. 2014a. LHON gene therapy vector prevents visual loss and optic neuropathy induced by G11778A mutant mitochondrial DNA: biodistribution and toxicology profile. Investig. Ophthalmol. Vis. Sci. 55:127739–53 [Google Scholar]
  102. Koilkonda RD, Yu H, Chou TH, Feuer WJ, Ruggeri M. et al. 2014b. Safety and effects of the vector for the Leber hereditary optic neuropathy gene therapy clinical trial. JAMA Ophthalmol. 132:4409–20 [Google Scholar]
  103. Kõks S, Overall RW, Ivask M, Soomets U, Guha M. et al. 2013. Silencing of the WFS1 gene in HEK cells induces pathways related to neurodegeneration and mitochondrial damage. Physiol. Genomics 45:5182–90 [Google Scholar]
  104. Kyriakouli DS, Boesch P, Taylor RW, Lightowlers RN. 2008. Progress and prospects: gene therapy for mitochondrial DNA disease. Gene Ther. 15:1017–23 [Google Scholar]
  105. La Morgia C, Achilli A, Iommarini L, Barboni P, Pala M. et al. 2008. Rare mtDNA variants in Leber hereditary optic neuropathy families with recurrence of myoclonus. Neurology 70:10762–70 [Google Scholar]
  106. La Morgia C, Carbonelli M, Barboni P, Sadun AA, Carelli V. 2014. Medical management of hereditary optic neuropathies. Front. Neurol. 5:141 [Google Scholar]
  107. Lam BL, Feuer WJ, Schiffman JC, Porciatti V, Vandenbroucke R. et al. 2014. Trial end points and natural history in patients with G11778A Leber hereditary optic neuropathy: preparation for gene therapy clinical trial. JAMA Ophthalmol. 132:4428–36 [Google Scholar]
  108. Lee S, Van Bergen NJ, Kong GY, Chrysostomou V, Waugh HS. et al. 2011. Mitochondrial dysfunction in glaucoma and emerging bioenergetic therapies. Exp. Eye Res. 93:2204–12 [Google Scholar]
  109. Leigh PN, Al-Sarraj S, DiMauro S. 2015. Subacute necrotising encephalomyelopathy (Leigh's disease; Leigh syndrome). J. Neurol. Neurosurg. Psychiatry 86:4363–65 [Google Scholar]
  110. Lenaers G, Hamel C, Delettre C, Amati-Bonneau P, Procaccio V. et al. 2012. Dominant optic atrophy. Orphanet J. Rare Dis. 7:46 [Google Scholar]
  111. Leonhard K, Guiard B, Pellecchia G, Tzagoloff A, Neupert W, Langer T. 2000. Membrane protein degradation by AAA proteases in mitochondria: extraction of substrates from either membrane surface. Mol. Cell 5:4629–38 [Google Scholar]
  112. Levin L, Blumberg A, Barshad G, Mishmar D. 2014. Mito-nuclear co-evolution: the positive and negative sides of functional ancient mutations. Front. Genet. 5:448 [Google Scholar]
  113. Levin LA. 2015. Superoxide generation explains common features of optic neuropathies associated with cecocentral scotomas. J. Neuroophthalmol. 35:2152–60 [Google Scholar]
  114. Li C-H, Cheng Y-W, Liao P-L, Yang Y-T, Kang J-J. 2010. Chloramphenicol causes mitochondrial stress, decreases ATP biosynthesis, induces matrix metalloproteinase-13 expression, and solid-tumor cell invasion. Toxicol. Sci. 116:1140–50 [Google Scholar]
  115. Lieber DS, Calvo SE, Shanahan K, Slate NG, Liu S. et al. 2013. Targeted exome sequencing of suspected mitochondrial disorders. Neurology 80:191762–70 [Google Scholar]
  116. Lill R. 2009. Function and biogenesis of iron–sulphur proteins. Nature 460:831–38 [Google Scholar]
  117. Lin W, Kuang H. 2014. Oxidative stress induces autophagy in response to multiple noxious stimuli in retinal ganglion cells. Autophagy 10:101692–701 [Google Scholar]
  118. Liu Y, Schmidt S, Qin X, Gibson J, Munro D. et al. 2007. No association between OPA1 polymorphisms and primary open-angle glaucoma in three different populations. Mol. Vis. 13:2137–41 [Google Scholar]
  119. Lodi R, Montagna P, Cortelli P, Iotti S, Cevoli S. et al. 2000. ‘Secondary’ 4216/ND1 and 13708/ND5 Leber's hereditary optic neuropathy mitochondrial DNA mutations do not further impair in vivo mitochondrial oxidative metabolism when associated with the 11778/ND4 mitochondrial DNA mutation. Brain 123:1896–902 [Google Scholar]
  120. Loiseau D, Chevrollier A, Verny C, Guillet V, Gueguen N. et al. 2007. Mitochondrial coupling defect in Charcot–Marie–Tooth type 2A disease. Ann. Neurol. 61:4315–23 [Google Scholar]
  121. Lu J, Holmgren A. 2014. The thioredoxin antioxidant system. Free Radic. Biol. Med. 66:75–87 [Google Scholar]
  122. Luca CC, Lam BL, Moraes CT. 2004. Erythromycin as a potential precipitating agent in the onset of Leber's hereditary optic neuropathy. Mitochondrion 4:131–36 [Google Scholar]
  123. Luzhansky JZ, Pierce AB, Hoy JF, Hall AJ. 2001. Leber's hereditary optic neuropathy in the setting of nucleoside analogue toxicity. AIDS 15:121588–89 [Google Scholar]
  124. Macedo-Souza LI, Kok F, Santos S, Amorim SC, Starling A. et al. 2005. Spastic paraplegia, optic atrophy, and neuropathy is linked to chromosome 11q13. Ann. Neurol. 57:5730–37 [Google Scholar]
  125. Mackey DA, Fingert JH, Luzhansky JZ, McCluskey PJ, Howell N. et al. 2003. Leber's hereditary optic neuropathy triggered by antiretroviral therapy for human immunodeficiency virus. Eye 17:3312–17 [Google Scholar]
  126. Maio N, Rouault TA. 2014. Iron–sulfur cluster biogenesis in mammalian cells: new insights into the molecular mechanisms of cluster delivery. Biochim. Biophys. Acta 1853:1493–512 [Google Scholar]
  127. Mancuso M, Filosto M, Orsucci D, Siciliano G. 2008. Mitochondrial DNA sequence variation and neurodegeneration. Hum. Genomics 3:171–78 [Google Scholar]
  128. Marchbank NJ, Craig JE, Leek JP, Toohey M, Churchill AJ. et al. 2002. Deletion of the OPA1 gene in a dominant optic atrophy family: evidence that haploinsufficiency is the cause of disease. J. Med. Genet. 39:8e47 [Google Scholar]
  129. McFarland R, Turnbull DM. 2009. Batteries not included: diagnosis and management of mitochondrial disease. J. Intern. Med. 265:2210–28 [Google Scholar]
  130. McKee EE, Ferguson M, Bentley AT, Marks TA. 2006. Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones. Antimicrob. Agents Chemother. 50:62042–49 [Google Scholar]
  131. Mercimek-Mahmutoglu S, Tucker T, Casey B. 2011. Phenotypic heterogeneity in two siblings with 3-methylglutaconic aciduria type I caused by a novel intragenic deletion. Mol. Genet. Metab. 104:3410–13 [Google Scholar]
  132. Metodiev MD, Gerber S, Hubert L, Delahodde A, Chretien D. et al. 2014. Mutations in the tricarboxylic acid cycle enzyme, aconitase 2, cause either isolated or syndromic optic neuropathy with encephalopathy and cerebellar atrophy. J. Med. Genet. 51:12834–38 [Google Scholar]
  133. Meyer E, Michaelides M, Tee LJ, Robson AG, Rahman F. et al. 2010. Nonsense mutation in TMEM126A causing autosomal recessive optic atrophy and auditory neuropathy. Mol. Vis. 16:650–64 [Google Scholar]
  134. Milea D, Sander B, Wegener M, Jensen H, Kjer B. et al. 2010. Axonal loss occurs early in dominant optic atrophy. Acta Ophthalmol. 88:3342–46 [Google Scholar]
  135. Milone M, Wang J, Liewluck T, Chen LC, Leavitt JA, Wong LJ. 2011. Novel POLG splice site mutation and optic atrophy. Arch. Neurol. 68:6806–11 [Google Scholar]
  136. Minegishi Y, Iejima D, Kobayashi H, Chi Z-L, Kawase K. et al. 2013. Enhanced optineurin E50K–TBK1 interaction evokes protein insolubility and initiates familial primary open-angle glaucoma. Hum. Mol. Genet. 22:173559–67 [Google Scholar]
  137. Misko A, Jiang S, Wegorzewska I, Milbrandt J, Baloh RH. 2010. Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. J. Neurosci. 30:124232–40 [Google Scholar]
  138. Miyama S, Arimoto K, Kimiya S, Tomi H. 2000. Complicated hereditary spastic paraplegia with peripheral neuropathy, optic atrophy, and mental retardation. Neuropediatrics 31:214–17 [Google Scholar]
  139. Morton S, Hesson L, Peggie M, Cohen P. 2008. Enhanced binding of TBK1 by an optineurin mutant that causes a familial form of primary open angle glaucoma. FEBS Lett. 582:6997–1002 [Google Scholar]
  140. Mozzillo E, Delvecchio M, Carella M, Grandone E, Palumbo P. et al. 2014. A novel CISD2 intragenic deletion, optic neuropathy and platelet aggregation defect in Wolfram syndrome type 2. BMC Med. Genet. 15:88 [Google Scholar]
  141. Nakaso K, Adachi Y, Fusayasu E, Doi K, Imamura K. et al. 2012. Leber's hereditary optic neuropathy with olivocerebellar degeneration due to G11778A and T3394C mutations in the mitochondrial DNA. J. Clin. Neurol. 8:3230–34 [Google Scholar]
  142. Navarro-Gomez D, Leipzig J, Shen L, Lott M, Stassen AP. et al. 2015. Phy-Mer: a novel alignment-free and reference-independent mitochondrial haplogroup classifier. Bioinformatics 31:1310–12 [Google Scholar]
  143. Newman NJ. 2005. Hereditary optic neuropathies: from mitochondria to the optic nerve. Am. J. Ophthalmol. 140:517–23 [Google Scholar]
  144. Newman NJ. 2011. Treatment of Leber hereditary optic neuropathy. Brain 134:2447–50 [Google Scholar]
  145. Newman NJ, Biousse V, Newman SA, Bhatti MT, Hamilton SR. et al. 2006. Progression of visual field defects in leber hereditary optic neuropathy: experience of the LHON treatment trial. Am. J. Ophthalmol. 141:61061–67 [Google Scholar]
  146. Nolden M, Ehses S, Koppen M, Bernacchia A, Rugarli EI, Langer T. 2005. The m-AAA protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria. Cell 123:2277–89 [Google Scholar]
  147. Olichon A, Landes T, Arnauné-Pelloquin L, Emorine LJ, Mils V. et al. 2007. Effects of OPA1 mutations on mitochondrial morphology and apoptosis: relevance to ADOA pathogenesis. J. Cell Physiol. 211:2423–30 [Google Scholar]
  148. Osaka M, Ito D, Yagi T, Nihei Y, Suzuki N. 2015. Evidence of a link between ubiquilin 2 and optineurin in amyotrophic lateral sclerosis. Hum. Mol. Genet. 24:61617–29 [Google Scholar]
  149. Osborne NN, Núñez-Álvarez C, del Olmo-Aguado S. 2014. The effect of visual blue light on mitochondrial function associated with retinal ganglions cells. Exp. Eye Res. 128:8–14 [Google Scholar]
  150. Paquay S, Benoit V, Wetzburger C, Cordonnier M, Meire F. et al. 2013. Uncommon Leber “plus” disease associated with mitochondrial mutation m.11778G>A in a premature child. J. Child Neurol. 29:8NP18–23 [Google Scholar]
  151. Park K-P, Kim H-S, Kim E-S, Park Y-E, Lee C-H, Kim D-S. 2011. SLC25A4 and C10ORF2 mutations in autosomal dominant progressive external ophthalmoplegia. J. Clin. Neurol. 7:125–30 [Google Scholar]
  152. Patten DA, Wong J, Khacho M, Soubannier V, Mailloux RJ. et al. 2014. OPA1-dependent cristae modulation is essential for cellular adaptation to metabolic demand. EMBO J. 33:222676–91 [Google Scholar]
  153. Payne M, Yang Z, Katz BJ, Warner JE, Weight CJ. et al. 2004. Dominant optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia: a syndrome caused by a missense mutation in OPA1. Am. J. Ophthalmol. 138:5749–55 [Google Scholar]
  154. Pesch UE, Leo-Kottler B, Mayer S, Jurklies B, Kellner U. et al. 2001. OPA1 mutations in patients with autosomal dominant optic atrophy and evidence for semi-dominant inheritance. Hum. Mol. Genet. 10:131359–68 [Google Scholar]
  155. Pfeffer G, Gorman GS, Griffin H, Kurzawa-Akanbi M, Blakely EL. et al. 2014. Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance. Brain 137:1323–36 [Google Scholar]
  156. Plant GT, Perry VH. 1990. The anatomical basis of the caecocentral scotoma. New observations and a review. Brain 113:1441–57 [Google Scholar]
  157. Pott JWR, Wong KH. 2006. Leber's hereditary optic neuropathy and vitamin B12 deficiency. Graefe's Arch. Clin. Exp. Ophthalmol. 244:1357–59 [Google Scholar]
  158. Puomila A, Huoponen K, Mäntyjärvi M, Hämäläinen P, Paananen R. et al. 2005. Dominant optic atrophy: correlation between clinical and molecular genetic studies. Acta Ophthalmol. Scand. 83:3337–46 [Google Scholar]
  159. Qi X, Lewin AS, Hauswirth WW, Guy J. 2003. Optic neuropathy induced by reductions in mitochondrial superoxide dismutase. Investig. Ophthalmol. Vis. Sci. 44:31088–96 [Google Scholar]
  160. Reis A, Mateus C, Viegas T, Florijn R, Bergen A. et al. 2013. Physiological evidence for impairment in autosomal dominant optic atrophy at the pre-ganglion level. Graefe's Arch. Clin. Exp. Ophthalmol. 251:1221–34 [Google Scholar]
  161. Reynier P, Amati-Bonneau P, Verny C, Olichon A, Simard G. et al. 2004. OPA3 gene mutations responsible for autosomal dominant optic atrophy and cataract. J. Med. Genet. 41:9e110 [Google Scholar]
  162. Rouzier C, Bannwarth S, Chaussenot A, Chevrollier A, Verschueren A. et al. 2012. The MFN2 gene is responsible for mitochondrial DNA instability and optic atrophy ‘plus’ phenotype. Brain 135:23–34 [Google Scholar]
  163. Ryu S-W, Jeong HJ, Choi M, Karbowski M, Choi C. 2010. Optic atrophy 3 as a protein of the mitochondrial outer membrane induces mitochondrial fragmentation. Cell Mol. Life Sci. 67:162839–50 [Google Scholar]
  164. Sadun AA, Carelli V, Salomao SR, Berezovsky A, Quiros PA. et al. 2003. Extensive investigation of a large Brazilian pedigree of 11778/haplogroup J Leber hereditary optic neuropathy. Am. J. Ophthalmol. 136:2231–38 [Google Scholar]
  165. Sadun AA, Win PH, Ross-Cisneros FN, Walker SO, Carelli V. 2000. Leber's hereditary optic neuropathy differentially affects smaller axons in the optic nerve. Trans. Am. Ophthalmol. Soc. 98:223–35 [Google Scholar]
  166. Santel A, Fuller MT. 2001. Control of mitochondrial morphology by a human mitofusin. J. Cell Sci. 114:867–74 [Google Scholar]
  167. Saracchi E, DiFrancesco JC, Brighina L, Marzorati L, Curtò NA. et al. 2013. A case of Leber hereditary optic neuropathy plus dystonia caused by G14459A mitochondrial mutation. Neurol. Sci. 34:3407–8 [Google Scholar]
  168. Sarzi E, Goffart S, Serre V, Chrétien D, Slama A. et al. 2007. Twinkle helicase (PEO1) gene mutation causes mitochondrial DNA depletion. Ann. Neurol. 62:6579–87 [Google Scholar]
  169. Sergouniotis PI, Perveen R, Thiselton DL, Giannopoulos K, Sarros M. et al. 2015. Clinical and molecular genetic findings in autosomal dominant OPA3-related optic neuropathy. Neurogenetics 16:169–75 [Google Scholar]
  170. Seyer LA, Galetta K, Wilson J, Sakai R, Perlman S. et al. 2013. Analysis of the visual system in Friedreich ataxia. J. Neurol. 260:92362–69 [Google Scholar]
  171. Shan Y, Napoli E, Cortopassi G. 2007. Mitochondrial frataxin interacts with IDS11 of the NFS1/ISCU complex and multiple mitochondrial chaperones. Hum. Mol. Genet. 16:929–41 [Google Scholar]
  172. Shankar SP, Fingert JH, Carelli V, Valentino ML, King TM. et al. 2008. Evidence for a novel X-linked modifier locus for Leber hereditary optic neuropathy. Ophthalmic Genet. 29:117–24 [Google Scholar]
  173. Shen X, Ying H, Qiu Y, Park JS, Shyam R. et al. 2011. Processing of optineurin in neuronal cells. J. Biol. Chem. 286:53618–29 [Google Scholar]
  174. Siciliano G, Tessa A, Petrini S, Mancuso M, Bruno C. et al. 2003. Autosomal dominant external ophthalmoplegia and bipolar affective disorder associated with a mutation in the ANT1 gene. Neuromuscul. Disord. 13:2162–65 [Google Scholar]
  175. Smirnova E, Griparic L, Shurland DL, van der Bliek AM. 2001. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol. Biol. Cell 12:82245–56 [Google Scholar]
  176. Soriano A, Miró O, Mensa J. 2005. Mitochondrial toxicity associated with linezolid. N. Engl. J. Med. 353:212305–6 [Google Scholar]
  177. Spiegel R, Mandel H, Saada A, Lerer I, Burger A. et al. 2014. Delineation of C12orf65-related phenotypes: a genotype–phenotype relationship. Eur. J. Hum. Genet. 22:81019–25 [Google Scholar]
  178. Spiegel R, Pines O, Ta-Shma A, Burak E, Shaag A. et al. 2012. Infantile cerebellar-retinal degeneration associated with a mutation in mitochondrial aconitase, ACO2. Am. J. Hum. Genet. 90:3518–23 [Google Scholar]
  179. Stone EM, Newman NJ, Miller NR, Johns DR, Lott MT, Wallace DC. 1992. Visual recovery in patients with Leber's hereditary optic neuropathy and the 11778 mutation. J. Clin. Neuroophthalmol. 12:110–14 [Google Scholar]
  180. Taanman J-W, Daras M, Albrecht J, Davie CA, Mallam EA. et al. 2009. Characterization of a novel TYMP splice site mutation associated with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Neuromuscul. Disord. 19:2151–54 [Google Scholar]
  181. Tan G, Napoli E, Taroni F, Cortopassi G. 2003. Decreased expression of genes involved in sulfur amino acid metabolism in frataxin-deficient cells. Hum. Mol. Genet. 12:1699–711 [Google Scholar]
  182. Tatsuta T, Langer T. 2009. AAA proteases in mitochondria: diverse functions of membrane-bound proteolytic machines. Res. Microbiol. 160:9711–17 [Google Scholar]
  183. Tazir M, Hamadouche T, Nouioua S, Mathis S, Vallat J-M. 2014. Hereditary motor and sensory neuropathies or Charcot–Marie–Tooth diseases: an update. J. Neurol. Sci. 347:14–22 [Google Scholar]
  184. Tchikviladzé M, Gilleron M, Maisonobe T, Galanaud D, Laforêt P. et al. 2015. A diagnostic flow chart for POLG-related diseases based on signs sensitivity and specificity. J. Neurol. Neurosurg. Psychiatry 86:646–54 [Google Scholar]
  185. Tezel G. 2006. Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences. Prog. Retin. Eye Res. 25:5490–513 [Google Scholar]
  186. Thiselton DL, Alexander C, Morris A, Brooks S, Rosenberg T. et al. 2001. A frameshift mutation in exon 28 of the OPA1 gene explains the high prevalence of dominant optic atrophy in the Danish population: evidence for a founder effect. Hum. Genet. 109:5498–502 [Google Scholar]
  187. Thiselton DL, Alexander C, Taanman J-W, Brooks S, Rosenberg T. et al. 2002. A comprehensive survey of mutations in the OPA1 gene in patients with autosomal dominant optic atrophy. Investig. Ophthalmol. Vis. Sci. 43:61715–24 [Google Scholar]
  188. Toomes C, Marchbank NJ, Mackey DA, Craig JE, Newbury-Ecob RA. et al. 2001. Spectrum, frequency and penetrance of OPA1 mutations in dominant optic atrophy. Hum. Mol. Genet. 10:131369–78 [Google Scholar]
  189. Tucker BA, Solivan-Timpe F, Roos BR, Anfinson KR, Robin AL. et al. 2014. Duplication of TBK1 stimulates autophagy in iPSC-derived retinal cells from a patient with normal tension glaucoma. J. Stem Cell Res Ther. 3:5161 [Google Scholar]
  190. Tuppen HA, Hogan VE, He L, Blakely EL, Worgan L. et al. 2010. The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple families. Brain 133:102952–63 [Google Scholar]
  191. Tyynismaa H, Suomalainen A. 2009. Mouse models of mitochondrial DNA defects and their relevance for human disease. EMBO Rep. 10:137–43 [Google Scholar]
  192. van der Bliek AM, Shen Q, Kawajiri S. 2013. Mechanisms of mitochondrial fission and fusion. Cold Spring Harb. Perspect. Biol. 5:6a011072 [Google Scholar]
  193. Van Goethem G, Mercelis R, Löfgren A, Seneca S, Ceuterick C. et al. 2003. Patient homozygous for a recessive POLG mutation presents with features of MERRF. Neurology 61:121811–13 [Google Scholar]
  194. Verny C, Amati-Bonneau P, Dubas F, Malthiéry Y, Reynier P, Bonneau D. 2005. Atrophie optique, cataracte et signes extra-pyramidaux par mutation du gène OPA3. Rev. Neurol. 161:4451–54 [Google Scholar]
  195. Votruba M, Fitzke FW, Holder GE, Carter A, Bhattacharya SS, Moore AT. 1998a. Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy. Arch. Ophthalmol. 116:3351–58 [Google Scholar]
  196. Votruba M, Moore AT, Bhattacharya SS. 1998b. Clinical features, molecular genetics, and pathophysiology of dominant optic atrophy. J. Med. Genet. 35:10793–800 [Google Scholar]
  197. Wang H-W, Jia X, Ji Y, Kong Q-P, Zhang Q. et al. 2008. Strikingly different penetrance of LHON in two Chinese families with primary mutation G11778A is independent of mtDNA haplogroup background and secondary mutation G13708A. Mutat. Res. 643:1–248–53 [Google Scholar]
  198. Waterham HR, Koster J, van Roermund CWT, Mooyer PA, Wanders RJ, Leonard JV. 2007. A lethal defect of mitochondrial and peroxisomal fission. N. Engl. J. Med. 356:1736–41 [Google Scholar]
  199. Wedding IM, Koht J, Tran GT, Misceo D, Selmer KK. et al. 2014. Spastic paraplegia type 7 is associated with multiple mitochondrial DNA deletions. PLOS ONE 9:1e86340 [Google Scholar]
  200. Weisenfeld NI, Yin S, Sharpe T, Lau B, Hegarty R. et al. 2014. Comprehensive variation discovery in single human genomes. Nat. Genet. 46:121350–55 [Google Scholar]
  201. Wiggs JL, Pierce EA. 2013. Genetic testing for inherited eye disease: who benefits?. JAMA Ophthalmol. 131:101265–66 [Google Scholar]
  202. Williams PA, Morgan JE, Votruba M. 2010. Opa1 deficiency in a mouse model of dominant optic atrophy leads to retinal ganglion cell dendropathy. Brain 133:102942–51 [Google Scholar]
  203. Williams PA, Piechota M, von Ruhland C, Taylor E, Morgan JE, Votruba M. 2012. Opa1 is essential for retinal ganglion cell synaptic architecture and connectivity. Brain 135:493–505 [Google Scholar]
  204. Wolf C, Gramer E, Müller-Myhsok B, Pasutto F, Reinthal E. et al. 2009. Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study. BMC Med. Genet. 10:91 [Google Scholar]
  205. Wong LJ. 2007. Pathogenic mitochondrial DNA mutations in protein-coding genes. Muscle Nerve 36:279–93 [Google Scholar]
  206. Wong YC, Holzbaur EL. 2014. Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. PNAS 111:42E4439–48 [Google Scholar]
  207. Wortmann SB, Duran M, Anikster Y, Barth PG, Sperl W. et al. 2013a. Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature: proper classification and nomenclature. J. Inherit. Metab. Dis. 36:6923–28 [Google Scholar]
  208. Wortmann SB, Kluijtmans LA, Rodenburg RJ, Sass JO, Nouws J. et al. 2013b. 3-Methylglutaconic aciduria—lessons from 50 genes and 977 patients. J. Inherit. Metab. Dis. 36:6913–21 [Google Scholar]
  209. Wortmann SB, Kremer BH, Graham A, Willemsen MA, Loupatty FJ. et al. 2010. 3-methylglutaconic aciduria type I redefined: a syndrome with late-onset leukoencephalopathy. Neurology 75:121079–83 [Google Scholar]
  210. Yunis AA. 1989. Chloramphenicol toxicity: 25 years of research. Am. J. Med. 87:3N44N–48N [Google Scholar]
  211. Yu Wai Man CY, Chinnery PF, Griffiths PG. 2005. Optic neuropathies—importance of spatial distribution of mitochondria as well as function. Med. Hypotheses 65:61038–42 [Google Scholar]
  212. Yu-Wai-Man P, Chinnery PF. 2013. Dominant optic atrophy: novel OPA1 mutations and revised prevalence estimates. Ophthalmology 120:81712–12.e1 [Google Scholar]
  213. Yu-Wai-Man P, Griffiths PG, Burke A, Sellar PW, Clarke MP. et al. 2010a. The prevalence and natural history of dominant optic atrophy due to OPA1 mutations. Ophthalmology 117:81538–46.e1 [Google Scholar]
  214. Yu-Wai-Man P, Griffiths PG, Chinnery PF. 2011a. Mitochondrial optic neuropathies—disease mechanisms and therapeutic strategies. Prog. Retin. Eye Res. 30:281–114 [Google Scholar]
  215. Yu-Wai-Man P, Griffiths PG, Gorman GS, Lourenco CM, Wright AF. et al. 2010b. Multi-system neurological disease is common in patients with OPA1 mutations. Brain 133:771–86 [Google Scholar]
  216. Yu-Wai-Man P, Griffiths PG, Hudson G, Chinnery PF. 2009. Inherited mitochondrial optic neuropathies. J. Med. Genet. 46:3145–58 [Google Scholar]
  217. Yu-Wai-Man P, Shankar SP, Biousse V, Miller NR, Bean LJ. et al. 2011b. Genetic screening for OPA1 and OPA3 mutations in patients with suspected inherited optic neuropathies. Ophthalmology 118:3558–63 [Google Scholar]
  218. Yu-Wai-Man P, Stewart JD, Hudson G, Andrews RM, Griffiths PG. et al. 2010c. OPA1 increases the risk of normal but not high tension glaucoma. J. Med. Genet. 47:2120–25 [Google Scholar]
  219. Zanna C, Ghelli A, Porcelli AM, Karbowski M, Youle RJ. et al. 2008. OPA1 mutations associated with dominant optic atrophy impair oxidative phosphorylation and mitochondrial fusion. Brain 131:352–67 [Google Scholar]
  220. Züchner S, De Jonghe P, Jordanova A, Claeys KG, Guergueltcheva V. et al. 2006. Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2. Ann. Neurol. 59:2276–81 [Google Scholar]
/content/journals/10.1146/annurev-vision-082114-035651
Loading
Mitochondrial Genetics and Optic Neuropathy
Annual Review of Vision Science 1, 97 (2015); https://doi.org/10.1146/annurev-vision-082114-035651
/content/journals/10.1146/annurev-vision-082114-035651
/content/journals/10.1146/annurev-vision-082114-035651
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error