Mitochondria and degenerative disorders
M. Orth
Dr. Michael Orth is a clinical neurologist and is currently completing his Ph.D. with Professor Schapira at the Department of Clinical Neurosciences, Royal Free and University College London Medical School. His main interests are molecular genetic aspects and the cell biology of alpha-synuclein.
Search for more papers by this authorCorresponding Author
A.H.V. Schapira
University Department of Clinical Neurosciences, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK.
University Department of Clinical Neurosciences, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK.Search for more papers by this authorM. Orth
Dr. Michael Orth is a clinical neurologist and is currently completing his Ph.D. with Professor Schapira at the Department of Clinical Neurosciences, Royal Free and University College London Medical School. His main interests are molecular genetic aspects and the cell biology of alpha-synuclein.
Search for more papers by this authorCorresponding Author
A.H.V. Schapira
University Department of Clinical Neurosciences, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK.
University Department of Clinical Neurosciences, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK.Search for more papers by this authorAbstract
In mammalian cells, mitochondria provide energy from aerobic metabolism. They play an important regulatory role in apoptosis, produce and detoxify free radicals, and serve as a cellular calcium buffer. Neurodegenerative disorders involving mitochondria can be divided into those caused by oxidative phosphorylation (OXPHOS) abnormalities either due to mitochondrial DNA (mtDNA) abnormalities, e.g., chronic external ophthalmoplegia, or due to nuclear mutations of OXPHOS proteins, e.g., complex I and II associated with Leigh syndrome. There are diseases caused by nuclear genes encoding non-OXPHOS mitochondrial proteins, such as frataxin in Friedreich ataxia (which is likely to play an important role in mitochondrial-cytosolic iron cycling), paraplegin (possibly a mitochondrial ATP-dependent zinc metalloprotease of the AAA-ATPases in hereditary spastic paraparesis), and possibly Wilson disease protein (an abnormal copper transporting ATP-dependent P-type ATPase associated with Wilson disease). Huntingon disease is an example of diseases with OXPHOS defects associated with mutations of nuclear genes encoding non-mitochondrial proteins such as huntingtin. There are also disorders with evidence of mitochondrial involvement that cannot as yet be assigned. These include Parkinson disease (where a complex I defect is described and free radicals are generated from dopamine metabolism), amyotrophic lateral sclerosis, and Alzheimer disease, where there is evidence to suggest mitochondrial involvement perhaps secondary to other abnormalities. © 2001 Wiley-Liss, Inc.
REFERENCES
- Adamec J, Rusnack F, Owen WG, Naylor S, Benson LM, Gacy AM, Isaya G. 2000. Iron-dependent self-assembly of recombinant yeast frataxin: implications for Friedreich's ataxia. Am J Hum Genet 67: 549–562.
- Alam ZI, Halliwell B, Jenner P. 2000. No evidence for increased oxidative damage to lipids, proteins, or DNA in Huntington's disease. J Neurochem 75: 840–846.
- Andreassen OA, Ferrante RJ, Klivenyi P, Klein AM, Shinobu LA, Epstein CJ, Beal MF. 2000. Partial deficiency of manganese superoxide dismutase exacerbates a transgenic mouse model of amyotrophic lateral sclerosis. Ann Neurol 47: 447–455.
- Arenas J, Campos Y, Ribacoba R, Martin MA, Rubio JC, Ablanedo P, Cabello A. 1998. Complex I defect in muscle from patients with Huntington's disease. Ann Neurol 43: 397–400.
- Babcock M, DeSilva D, Oaks R, Davis-Kaplan S, Jiralerspong S, Montermini L, Pandolfo M, Kaplan J. 1997. Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science 276: 1709–1712.
- Berman SB, Hastings TG. 1999. Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: implications for Parkinson's disease. J Neurochem 73: 1127–1137.
- Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. 2000. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 3: 1301–1306.
- Bonneau D, Rozet JM, Bulteau C, Berthier M, Mettey R, Gil R, Munnich A, LeMerrer M. 1993. X-linked spastic paraplegia (SPG2): clinical heterogeneity at a single gene locus. J Med Genet 30: 381–384.
- Borchelt DR, Guarnieri M, Wong PC, Lee MK, Slunt HS, Xu ZS, Sisodia SS, Price DL, Cleveland DW. 1995. Superoxide dismutase 1 subunits with mutations linked to familial amyotrophic lateral sclerosis do not affect wild-type subunit function. J Biol Chem 17: 3234–3238.
- Borthwick GM, Johnson MA, Ince PG, Shaw PJ, Turnbull DM. 1999. Mitochondrial enzyme activity in amyotrophic lateral sclerosis: implications for the role of mitochondria in neuronal cell death. Ann Neurol 46: 787–790.
- Bourgeron T, Rustin P, Chretien D, Birchmachin M, Bourgeois M, Viegaspequignot E, Munnich A, Rotig A. 1995. Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nature Genet 11: 144–149.
- Bradley J, Blake J, Chamberlain S, Thomas P, Cooper J, Schapira A. 2000. Clinical, biochemical and molecular genetic correlations in Friedreich's ataxia. Hum Mol Genet 9: 275–282.
- Browne SE, Bowling AC, MacGarvey U, Baik MJ, Berger SC, Muqit MMK, Bird ED, Beal MF. 1997. Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia. Ann Neurol 41: 646–653.
- Campuzano V, Montermini L, Molto' MD, Pianese L, Cassee M, Cavalcanti F, Monros E, Rodius F, Duclos F, Monticelli A, Zara F, Canizares J, Koutnikova H, Bidichandani SI, Gellera C, Brice A, Trouillas P, DeMichele G, Filla A, DeFrutos R, Palau F, Patel PI, DiDonato S, Mandel JL, Cocozza S, Koenig M, Pandolfo M. 1996. Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271: 1423–1427.
- Campuzano V, Montermini L, Lutz Y, Cova L, Hindelang C, Jiralerspong S, Trottier Y, Kish SJ, Faucheux B, Trouillas P, Authier FJ, Durr A, Mandel JL, Vescovi A, Pandolfo M, Koeing M. 1997. Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum Mol Genet 6: 1771–1780.
- Carri MT, Ferri A, Battistoni A, Famhy L, Gabbianelli R, Poccia F, Rotilio G. 1997. Expression of a Cu,Zn superoxide dismutase typical of familial amyotrophic lateral sclerosis induces mitochondrial alteration and increase of cytosolic Ca2+ concentration in transfected neuroblastoma SH-SY5Y cells. FEBS Lett 414: 365–368.
- Carriedo SG, Sensi SL, Yin HZ, Weiss JH. 2000. AMPA exposures induce mitochondrial Ca(2+) overload and ROS generation in spinal motor neurons in vitro. J Neurosci 20: 240–250.
- Casari G, De Fusco M, Ciarmatori S, Zeviani M, Mora M, Fernandez P, De Michele G, Filla A, Cocozza S, Marconi R, Dürr A, Fontaine B, Ballabio A. 1998. Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell 93: 973–983.
- Chandrasekaran K, Hatanpää K, Rapoport SI, Brady DR. 1997. Decreased expression of nuclear and mitochondrial DNA-encoded genes of oxidative phosphorylation in association neocortex in Alzheimer disease. Mol Brain Res 44: 99–104.
- Ciriolo MR, De Martino A, Lafavia E, Rossi L, Carri MT, Rotilio G. 2000. Cu,Zn-superoxide dismutase-dependent apoptosis induced by nitric oxide in neuronal cells. J Biol Chem 275: 5065–5072.
- Cohen G, Farooqui R, Kesler N. 1997. Parkinson's disease: a new link between monoamine oxidase and mitochondrial electron flow. Proc Natl Acad Sci U S A 94: 4890–4894.
- Dabbeni-Sala F, Di Santo S, Franceshini D, Skaper SD, Giusti P. 2001. Melatonin protects against 6-OHDA-induced neurotoxicity in rats: a role for mitochondrial complex I activity. FASEB J 15: 164–170.
- Davies SW, Turmaine M, Cozens BA, DiDiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP. 1997. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90: 537–548.
- Davis RE, Miller S, Hermstadt C, Ghosh SS, Fahy E, Shinobu LA, Galasko D, Thal LJ, Beal MF, Howell N, Parker WD Jr. 1997. Mutations in mitochondrial cytochrome c oxidase genes segregate with late-onset Alzheimer's disease. Proc Natl Acad Sci U S A 94: 4526–4531.
- De Michele G, De Fusco M, Cavalcanti F, Filla A, Marconi R, Volpe G, Monticelli A, Ballabio A, Casari G, Cocozza S. 1998. A new locus for autosomal recessive hereditary spastic paraplegia maps to chromosome 16q24.3. Am J Hum Genet 63: 135–139.
- Delettre C, Lenaers G, Griffoin JM, Gigarel N, Lorenzo C, Belenguer P, Pelloquin L, Grosgeorge J, Turc-Carel C, Perret E, Astarie-Dequeker L, Lasquellec B, Arnaud B, Ducommun J, Kaplan CP. 2000. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nature Genet 26: 207–210.
- Dexter DT, Holley AE, Flitter WD, Slater TF, Wells FR, Daniel SE, Lees AJ, Jenner P, Marsden CD. 1994. Increased levels of lipid hydroperoxides in the Parkinsonian substantia nigra: an HPLC and ESR study. Mov Disord 9: 92–97.
- Dhaliwal GK, Grewal RP. 2000. Mitochondrial DNA deletion mutation levels are elevated in ALS brains. Neuroreport 11: 2507–2509.
- DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N. 1997. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 26: 1990–1993.
- DiMauro S, Schon EA. 2001. Mitochondrial DNA mutations in human disease. Am J Med Genet, this issue.
- Filla A, De Michele G, Marconi R, Bucci L, Carillo C, Castellano AE, Iorio L, Kniahynicki C, Rossi F, Campanella G. 1992. Prevalence of hereditary ataxias and spsatic paraplegias in Molise, a region of Italy. J Neurol 239: 351–353.
- Fink JK. 1997. Advances in hereditary spastic paraplegia. Curr Opin Neurol 10: 313–318.
- Fink JK, Wu C-tB, Jones SM, Sharp GB, Lange BM, Lesicki A, Reinglass T, Varvil T, Otterud B, Leppert M. 1995. Autosomal dominant spastic paraplegia: tight linkage to chromosome 15q. Am J Hum Genet 56: 188–192.
- Foury F. 1999. Low iron concentration and aconitase deficiency in a yeast frataxin homologue deficient strain. FEBS Lett 456: 281–284.
- Friedlander RM, Brown RH, Gagliardini V, Wang J, Yuan J. 1997. Inhibition of ICE slows ALS in mice. Nature 388: 31.
- Gabbianelli R, Ferri A, Rotilio G, Carri MT. 1999. Aberrant copper chemistry as a major mediator of oxidative stress in a human cellular model of amyotrophic lateral sclerosis. J Neurochem 73: 1175–1180.
- Gigli GL, Diomedi M, Bernardi G, Placidi F, Marciani MG, Calia E, Maschio MCE, Neri G. 1993. Spastic paraplegia, epilepsy, and mental retardation in several members of a family: a novel genetic disorder. Am J Med Genet 45: 711–716.
- Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, Mant R, Newton P, Rooke K, Roques P, Talbot C, Pericak-Vance M, Roses A, Williamson R, Rossor M, Owen M, Hardy J. 1991. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349: 704–706.
- Good PF, Werner P, Hsu A, Olanow CW, Perl DP. 1996. Evidence of neuronal oxidative damage in Alzheimer's disease. Am J Pathol 149: 21–28.
- Graham DG. 1978. Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 14: 633–643.
- Graham DG, Tiffany S, Bell WR, Gutknecht WF. 1978. Autooxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6-hydroxydopamine and related compounds toward C1300 neuroblastoma cell in-vitro. Mol Phamacol 14: 644–653.
- Gu M, Cooper JM, Gash M, Mann VM, Javoy-Agid F, Schapira AHV. 1996. Mitochondrial defect in Huntington's disease caudate nucleus. Ann Neurol 39: 385–389.
- Gu M, Owen AD, Toffa SEK, Cooper JM, Dexter DT, Jenner P, Marsden CD, Schapira AHV. 1998. Mitochondrial function, GSH and iron in neurodegeneration and Lewy body diseases. J Neurol Sci 158: 24–29.
- Gu M, Cooper JM, Butler P, Walker AP, Mistry PK, Dooley JS, Schapira AHV. 2000. Oxidative-phosphorylation defects in liver of patients with Wilson's disease. Lancet 356: 469–474.
- Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, Caliendo J, Hentati A, Kwon YW, Deng HX, Chen WJ, Zhai P, Sufit RL, Siddique T. 1994. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264: 1772–1775.
- Gutekunst CA, Li SH, Yi H, Mulroy JS, Kuemmerle S, Jones R, Rye D, Ferrante RJ, Hersch SM, Li XJ. 1999. Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology. J Neurosci 19: 2522–2534.
- Gutteridge JM, Halliwell B. 1989. Iron toxicity and oxygen radicals. Baillieres Clin Haematol 2: 195–256.
- Harding AE. 1981a. Friedreich's Ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain 104: 598–620.
- Harding AE. 1981b. Genetic aspects of autosomal dominant late onset cerebellar ataxia. J Med Genet 18: 436–441.
- Hayakawa M, Hattori K, Sugiyama S, Ozawa T. 1991. Age-associated accumulation of 8-hydroxydeoxyguanosine in mitochondrial DNA of human diaphragm. Biochem Biophys Res Commun 179: 1023–1029.
- Hayakawa M, Hattori K, Sugiyama S, Ozawa T. 1992. Age-associated oxygen damage and mutations in mitochondrial DNA in human hearts. Biochem Biophys Res Commun 189: 979–985.
- Hazan J, Lamy C, Melki J, Munnich A, de Recondo J, Weissenbach J. 1993. Autosomal dominant familial spastic paraplegia is genetically heterogenous and one locus maps to chromosome 14q. Nature Genet 5: 163–167.
- Hazan J, Fontaine B, Bruyn RPM, Lamy C, van Deutekom JCT, Rime CS, Dürr A, Melki J, Lyon-Caen O, Agid Y. 1994. Linkage of a new locus for autosomal dominant familial spastic paraplegia to chromosome 2p. Hum Mol Genet 3: 1569–1573.
- Hentati A, Pericak-Vance MA, Hung WY, Belal S, Laing N, Boustany RM, Hentati F, Ben-Hamida M, Siddique T. 1994. Linkage of “pure” autosomal recessive familial spastic paraplegia to chromosome 8 markers and evidence of genetic loci heterogeneity. Hum Mol Genet 3: 1263–1267.
- Hirano M, Shtilbans A, Mayeux R, Davidson MM, DiMauro S, Knowles JA, Schon E A. 1997. Apparent mtDNA heteroplasmy in Alzheimer's disease patients and in normals due to PCR amplification of nucleus-embedded mtDNA pseudogenes. Proc Natl Acad Sci U S A 94: 14894–14899.
- Hornykiewicz O, Kish SJ. 1987. Biochemical pathophysiology of Parkinson's disease. Adv Neurol 45: 19–34.
- Hung IH, Suzuki M, Yamaguchi Y, Yuan DS, Klausner RD, Gitlin JD. 1997. Biochemical characterization of the Wilson disease protein and functional expression in the yeast Saccharomyces cerevisiae. J Biol Chem 272: 21461–21466.
- Huntington's Disease Collaborative Group. 1993. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72: 971–983.
- Jenkins BG, Rosas HD, Chen YC, Makabe T, Myers R, MacDonald M, Rosen BR, Beal MF, Koroshetz WJ. 1998. 1H NMR spectroscopy studies of Huntington's disease: correlations with CAG repeat numbers. Neurology 50: 1357–1365.
- Jouet M, Rosenthal A, Armstrong G, MacFarlane J, Stevenson R, Paterson J, Metzenberg A, Ionasescu V, Temple K, Kenwrick S. 1994. X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene. Nature Genet 7: 402–407.
- Kael EC, Vlug AS, Versieljen MW, Kullman M, Joosten EA, Bar PR. 2000. Chronic mitochonrial inhibition induces selective motoneuron death in vitro: a new model for amyotrophic lateral sclerosis. J Neurochem 74: 1158–1165.
- Katzman R. 1986. Alzheimer's disease. N Engl J Med 10: 964–973.
- Kim KJ, Jang YY, Han ES, Lee CS. 1999. Modulation of brain mitochondrial membrane permeability and synaptosomal Ca2+ transport by dopamine oxidation. Mol Cell Biochem 201: 89–98.
- Kish SJ, Bergeron C, Rajput A, Dozic S, Mastrogiacomo F, Chang LJ, Wilson JM, DiStefano LM, Nobrega JN. 1992. Brain cytochrome oxidase in Alzheimer's disease. J Neurochem 59: 776–779.
- Kish SJ, Mastrogiacomo F, Guttman M, Furukawa Y, Taanman JW, Dozic S, Pandolfo M, Lamarche J, DiStefano L, Chang LJ. 1999. Decreased brain protein levels of cytochrome oxidase subunits in Alzheimer's disease and in hereditary spinocerebellar ataxia disorders: a nonspecific change? J Neurochem 72: 700–707.
- Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N. 1998. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392: 605–608.
- Klivenyi P, Andreasson OA, Ferrante RJ, Dedeoglu A, Mueller G, Lancelot E, Bogdanov M, Anderson JK, Jiang D, Beal FM. 2000. Mice deficient in cellular glutathion peroxidase show increased vulnerability to malonate, 3-nitropropionic acid, and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. J Neurosci 20: 1–7.
- Koehler CM, Leuenberger D, Merchant S, Renold A, Junne T, Schatz G. 1999. Human deafness dystonia syndrome is a mitochondrial disease. Proc Natl Acad Sci U S A 96: 2141–2146.
- Kong J, Xu Z. 1998. Massive mitochondrial degeneration in motor neurons triggers the onset of amyotrophic lateral sclerosis in mice expressing a mutant SOD1. J Neurosci 18: 3241–3250.
- Koroshetz WJ, Jenkins BG, Rosen BR, Beal MF. 1997. Energy metabolism defects in Huntington's disease and effects of coenzyme Q10. Ann Neurol 41: 160–165.
- Kosel S, Egensperger R, Schnopp NM, Graeber MB. 1997. The ‘common deletion’ is not increased in parkinsonian substantia nigra as shown by competitive polymerase chain reaction. Mov Disord 12: 639–645.
- Kosel S, Grasbon-Frodl EM, Mautsch U, Egensperger R, von Eitzen U, Frishman D, Hofmann S, Gerbitz KD, Mehraein P, Graeber MB. 1998. Novel mutations of mitochondrial complex I in pathologically proven Parkinson disease. Neurogenetics 1: 197–204.
- Kostic V, Jackson-Lewis V, de Bilbao F, Dubois-Dauphin M, Przedborski S. 1997. Bcl-2: prolonging life in a transgenic mouse model of familial amyotrophic lateral sclerosis. Science 25: 559–562.
- Koutnikova H, Campuzano V, Foury F, Dolle' P, Cazzalini O, Koenig M. 1997. Studies of human, mouse and yeast homologoues indicate a mitochondrial function for frataxin. Nature Genet 16: 345–351.
- Kruger R, Kuhn W, Muller T, Woitalla D, Graber M, Kosel S, Przuntek H, Epplen JT, Schols L, Riess O. 1998. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nature Genet 18: 106–108.
- La Fontaine MA, Geddes JW, Banks A, Butterfield DA. 2000. Effects of endogenous and exogenous antioxidants on 3-nitropropionic acid -induced in vivo oxidative stress and striatal lesions: insight into Huntington's disease. J Neurochem 75: 1709–1715.
- Lamarche JB, Cote M, Lemieux B. 1980. The cardiomyopathy of Friedreich's ataxia morphological observations in 3 cases. Can J Neurol Sci 7: 389–396.
- Langston JW, Ballard P, Tetrud JW, Irwin I. 1983. Chronic parkinsonism in humans due to a product of meperidine analog synthesis. Science 219: 979–980.
- Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, Harta G, Brownstein MJ, Jonnalagada S, Chernova T, Dehejia A, Lavedan C, Gasser T, Steinbach PJ, Wilkinson KD, Polymeropoulos MH. 1998. The ubiquitin pathway in Parkinson's disease. Nature 395: 451–452.
- Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell H, Yu C, Jondro PD, Schmidt SD, Wang K, Crowley AC, Fu YH, Guenette SY, Galas D, Nemens E, Wijsman EM, Bird TD, Schellenberg GD, Tanzi RE. 1995. Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science 269: 973–977.
- Li H, Li SH, Cheng AL, Mangiarini L, Bates GP, Li XJ. 1999. Ultrastructural localization and progressive formation of neuropil aggregates in Huntington's disease transgenic mice. Hum Mol Genet 8: 1227–1236.
- Li H, Li SH, Johnston H, Shelbourne PF, Li XJ. 2000. Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity. Nature Genet 25: 385–389.
- Lizcano-Gil LA, Garcia-Cruz D, del Pilar Bernal-Beltran M, Hernandez A. 1997. Association of late onset spastic paraparesis and dementia: probably an autosomal dominant form of complicated paraplegia. Am J Med Genet 68: 1–6.
10.1002/(SICI)1096-8628(19970110)68:1<1::AID-AJMG1>3.0.CO;2-V CASPubMedWeb of Science®Google Scholar
- Lodi R, Cooper JM, Bradley JL, Manners D, Styles P, Taylor DJ, Schapira AHV. 1999. Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia. Proc Natl Acad Sci U S A 96: 11492–11495.
- Lodi R, Hart PE, Rajagopalan B, Taylor DJ, Crilley JG, Bradley JL, Blamire AM, Manners D, Styles P, Schapira AHV, Cooper JM. 2001. Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in patients with Friedreich's ataxia. Ann Neurol, in press.
- Loeffen J, Smeitink J, Triepels R, Smeets R, Schuelke M, Sengers R, Trijbels F, Hamel B, Mullart R, van den Heuvel L. 1998. The first nuclear-encoded complex I mutation in a patient with Leigh syndrome. Am J Hum Genet 63: 1598–1608.
- Lutsenko S, Cooper MJ. 1998. Localization of the Wilson's disease protein product to mitochondria. Proc Natl Acad Sci U S A 95: 6004–6009.
- Mann VM, Cooper JM, Javoy-Agid F, Agid Y, Jenner P, Schapira AHV. 1990. Mitochondrial function and parental sex effect in Huntington's disease. Lancet 336: 749.
- Martin LJ. 1999. Neuronal death in amyotrophic lateral sclerosis is apoptosis: possible contribution of a programmed cell death mechanism. J Neuropathol Exp Neurol 58: 459–471.
- Mayr-Wohlfart U, Rodel G, Henneberg A. 1997. Mitochondrial tRNA(Gln) and tRNA(Thr) gene variants in Parkinson's disease. Eur J Med Res 24: 111–113.
- McLaughlin BA, Nelson D, Erecinska M, Chesselet MF. 1998. Toxicity of dopamine to striatal neurons in vitro and potentiation of cell death by a mitochondrial inhibitor. J Neurochem 70: 2406–2415.
- Mecocci P, MacGarvey U, Kaufman AE, Koontz D, Shoffner JM, Wallace DC, Beal MF. 1993. Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. Ann Neurol 34: 606–616.
10.1002/ana.410340416 Google Scholar
- Michel PP, Hefti F. 1990. Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in culture. J Neurosci Res 26: 428–435.
- Mizuno Y, Saitoh T, Sone N. 1987. Inhibition of mitochondrial NADH-ubiquinone oxidoreductase activity by 1-methyl-phenylpyridinium ion. Biochem Biophys Res Commun 143: 294–299.
- Murata Y, Yamakawa E, Iizuka T, Kodama H, Abe T, Seki Y, Kodama M. 1995. Failure of copper incorporation into ceruloplasmin in the Golgi apparatus of LEC rat hepatocytes. Biochem Biophys Res Commun 209: 349–355.
- Musco G, Stier G, Kolmerer B, Adinolfi S, Martin S, Frenkiel T, Gibson T, Pastore A. 2000. Towards a structural understanding of Friedreich's ataxia: the solution structure of frataxin. Structure Fold Des 8: 695–707.
- Nagano K, Nakamura K, Urakami KI, Umeyama K, Uchiyama H, Koiwai K, Hattori S, Yamamoto T, Matsuda I, Endo F. 1998. Intracellular distribution of the Wilson's disease gene product (ATPase7B) after in vitro and in vivo exogenous expression in hepatocytes from the LEC rat, an animal model of Wilson's disease. Hepatology 27: 799–807.
- Nicklas WJ, Vyas I, Heikkila RE. 1985. Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. Life Sci 36: 2503–2508.
- Papadopoulou LC, Sue CM, Davidson MM, Tanji K, Nishino I, Sadlock JE, Krishna S, Walker W, Selby J, Glerum DM, Coster RV, Lyon G, Scalais E, Lebel R, Kaplan P, Shanske S, De Vivo DC, Bonilla E, Hirano M, DiMauro S, Schon EA. 1999. Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene. Nature Genet 23: 333–337.
- Parker WD Jr, Parks JK. 1995. Cytochrome c oxidase in Alzheimer's disease brain: purification and characterization. Neurology 45: 482–486.
- Parker WD Jr, Filley CM, Parks JK. 1990. Cytochrome oxidase deficiency in Alzheimer's disease. Neurology 40: 1302–1303.
- Parker WD Jr, Parks J, Filley CM, Kleinschmidt-DeMasters BK. 1994. Electron transport chain defects in Alzheimer's disease brain. Neurology 44: 1090–1096.
- Parkinson's Disease Study Group. 1993. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med 328: 176–183.
- Perez-Severiano F, Rios C, Segovia J. 2000. Striatal oxidative damage parallels the expression of a neurological phenotype in mice transgenic for the mutation of Huntington's disease. Brain Res 862: 234–237.
- Polidori MC, Mecocci P, Browne SE, Senin U, Beal MF. 1999. Oxidative damage to mitochondrial DNA in Huntington's disease parietal cortex. Neurosci Lett 272: 53–56.
- Polo JM, Calleja J, Combarros O, Berciano J. 1993. Hereditary “pure” spastic paraplegia: a study of nine families. J Neurol Neurosurg Psychiatry 56: 175–181.
- Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekhrappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoison RC, Di G, Golbe LI, Nussbaum RL. 1997. Mutation in the α-synuclein gene identified in families with Parkinson's disease. Science 276: 2045–2047.
- Radisky DC, Babcock MC, Kaplan J. 1999. The yeast frataxin homologue mediates mitochondrial iron efflux. J Biol Chem 274: 4497–4499.
- Raha S, Robinson BH. 2001. Mitochondria, oxygen free radicals and apoptosis. Am J Med Genet, this issue.
- Ramsay RR, Singer TP. 1986. Energy dependent uptake of N-methyl-4-phenylpyridinium, the neurotoxic metabolite of 1-methyl-4phenyl 1,2,3,6 tetrahydropyridine, by mitochondria. J Biol Chem 261: 7585–7587.
- Reaume AG, Elliott JL, Hoffman EK, Kowall NW, Ferrante RJ, Siwek DF, Wilcox HM, Flood DG, Beal MF, Brown RH Jr, Scott RW, Snider WD. 1996. Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury. Nature Genet 13: 43–47.
- Reid E. 1997. Pure hereditary spastic paraplegia. J Med Genet 34: 499–503.
- Rogaev EI, Sherrington R, Rogaeva EA, Levesque G, Ikeda M, Liang Y, Chi H, Lin C, Holman K, Tsuda T, Mar L, Sorbi S, Nacmias B, Piacentini S, Amaducci L, Chumakov I, Cohen D, Lannfelt L, Fraser PE, Rommens JM, St George-Hyslop PH. 1995. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 376: 775–778.
- Rotig A, Lonlay Pd, Chretien D, Foury F, Koenig M, Sidi D, Munnich A, Rustin P. 1997. Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia. Nature Genet 17: 215–217.
- Rustin P, von Kleist-Retzow JC, Chantrel-Groussard K, Sidi D, Munnich A, Rotig A. 1999. Effect of idebenone on cardiomyopathy in Friedreich's ataxia: a preliminary study. Lancet 354: 477–479.
- Sanchez-Ramos J, Övervik E, Ames BN. 1994. A marker of oxydoradical-mediated DNA damage (8-hydroxy-2′deoxyguanosine) is increased in nigro-striatum of Parkinson's disease brain. Neurodegeneration 3: 197–204.
- Sasaki S, Maruyama S, Yamane K, Sakuma H, Takeishi M. 1990. Ultrastructure of swollen proximal axons of anterior horn neurons in motor neuron disease. J Neurol Sci 97: 233–240.
- Saugier-Veber P, Munnich A, Bonneau D, Rozet JM, LeMerrer M, Gil R, Boespflug-Tanguy O. 1994. X-linked spastic paraplegia and Pelizaeus-Merzbacher disease are allelic at the proteolipid protein locus. Nature Genet 6: 257–262.
- Sawa A, Wiegand GW, Cooper J, Margolis RL, Sharp AH, Lawler JF Jr, Greenamyre T, Snyder SH, Ross CA. 1999. Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarisation. Nature Med 5: 1194–1198.
- Schaefer M, Roelofsen H, Wolters H, Hofmann WJ, Muller M, Kuipers F, Stremmel W, Vonk RJ. 1999. Localization of the Wilson's disease protein in human liver. Gastroenterology 117: 1380–1385.
- Schapira AHV, Mann VM, Cooper JM, Dexter D, Daniel SE, Jenner P, Clark JB, Marsden CD. 1990. Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson's disease. J Neurochem 55: 2142–2145.
- Schapira AH, Gu M, Taanman JW, Tabrizi SJ, Seaton T, Cleeter M, Cooper JM. 1998. Mitochondria in the etiology and pathogenesis of Parkinson's disease. Ann Neurol 44 (Suppl 1): S89–S98.
- Schilling G, Becher MW, Sharp AH, Jinnah HA, Duan K, Kotzuk JA, Slunt HH, Ratovitski T, Cooper JK, Jenkins NA, Copeland NG, Price DL, Ross CA, Borchelt DR. 1999. Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum Mol Genet 8: 397–407.
- Schuelke M, Smeitink J, Mariman E, Loeffen J, Plecko B, Trijbels F, Stockler-Ipsiroglu S, van den Heuvel L. 1999. Mutant NDUFV1 subunit of mitochondrial complex I causes leukodystrophy and myoclonic epilepsy. Nature Genet 21: 260–261.
- Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, Ysuda T, Mar L, Foncin JF, Bruni AC, Montesi MP, Sorbi S, Rainero I, Pinessi L, Nee L, Chumakov I, Pollen D, Broojes S, Sanseau P, Polinsky RJ, Wasco W, DaSilva HAR, Haines JL, Perocak-Vance MA, Tanzi RE, Roses AD, Fraser PE, Rommens JM, St SGeorge-Hyslop PH. 1995. Cloning of a gene bearing missense mutation in early-onset familial Alzheimer's disease. Nature 375: 754–760.
- Shimura-Miura H, Hattori N, Kang D, Miyako K, Nakabeppu Y, Mizuno Y. 1999. Increased 8-oxo-dGTPase in the mitochondria of substantia nigra neurons in Parkinson's disease. Ann Neurol 46: 920–924.
- Shoubridge EA. 2001. Cytochrome c oxidase deficiency. Am J Med Genet, this issue.
- Siklos L, Engelhardt J, Harati Y, Smith RG, Joo F, Appel SH. 1996. Ultrastructural evidence for altered calcium in motor nerve terminals in amyotropic lateral sclerosis. Ann Neurol 39: 203–216.
- Simon DK, Mayeux R, Marder K, Kowall NW, Beal MF, Johns DR. 2000. Mitochondrial DNA mutations in complex I and tRNA genes in Parkinson's disease. Neurology 54: 703–709.
- Smith MA, Perry G, Richey PL, Sayre LM, Anderson VE, Beal MF, Kowall N. 1996. Oxidative damage in Alzheimer's. Nature 382: 120–121.
- Sokol RJ, Devereaux M, Mierau GW, Hambidge KM, Shikes RH. 1990. Oxidant injury to hepatic mitochondrial lipids in rats with dietary copper overload. Modification by vitamin E deficiency. Gastroenterology 99: 1061–1071.
- Sokol RJ, Twedt D, McKim JM Jr, Devereaux MW, Karrer FM, Kam I, von Steigman G, Narkewicz MR, Bacon BR, Britton RS, Neuschwander-Tetri BA. 1994. Oxidant injury to hepatic mitochondria in patients with Wilson's disease and Bedlington terriers with copper toxicosis. Gastroenterology 107: 1788–1798.
- Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. 1997. Alpha-synuclein in Lewy bodies. Nature 388: 839–840.
- Sternlieb I. 1992. Fraternal concordance of types of abnormal hepatocellular mitochondria in Wilson's disease. Hepatology 16: 728–732.
- Sternlieb I, Quintana N, Volenberg I, Schilsky ML. 1995. An array of mitochondrial alterations in the hepatocytes of Long-Evans Cinnamon rats. Hepatology 22: 1782–1787.
- Swerdlow RH, Parks JK, Miller SW, Tuttle JB, Trimmer PA, Sheehan JP, Bennett JP, Davies RE, Parker WD. 1996. Origin and functional consequences of the complex i defect in Parkinson's disease. Ann Neurol 40: 663–671.
- Swerdlow RH, Parks JK, Cassarino DS, Maguire DJ, Maguire RS, Bennett JP Jr, Davis RE, Parker WD Jr. 1997. Cybrids in Alzheimer's disease: a cellular model of the disease? Neurology 49: 918–925.
- Swerdlow RH, Parks JK, Cassarino DS, Shilling AT, Bennet JP Jr, Harrison MB, Parker WD. 1999. Characterization of cybrid cell lines containing mtDNA from Huntington's disease patients. Biochem Biophys Res Commun 261: 701–704.
- Tabrizi SJ, Cleeter M, Xuereb J, Taanman JW, Cooper JM, Schapira AHV. 1999. Biochemical abnormalities and excitotoxicity in Huntington's disease brain. Ann Neurol 45: 25–32.
- Tabrizi SJ, Workman J, Hart PE, Mangiarini L, Mahal A, Bates G, Cooper JM, Schapira AH. 2000. Mitochondrial dysfunction and free radical damage in the Huntington R6/2 trangenic mouse. Ann Neurol 47: 80–86.
- Tanaka M, Sotomatsu A, Kanai H, Hirai S. 1991. Dopa and dopamine cause cultured neuronal death in the presence of iron. J Neurol Sci 101: 198–203.
- Tanner CM, Ottman R, Goldman SM, Ellenberg J, Chan P, Mayeux R, Langston JW. 1999. Parkinson disease in twins: an etiologic study JAMA 281: 341–346.
- Tiranti V, Hoertnagel K, Carrozzo R, Galimberti C, Munaro M, Granatiero M, Zelante L, Gasparini P, Marzella R, Rocchi M, Bayona-Bafaluy MP, Enriquez JA, Uziel G, Bertini E, Dionisi-Vici C, Franco B, Meitinger T, Zeviani M. 1998. Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency. Am J Hum Genet 63: 1609–1621.
- Triepels RH, van den Heuvel LP, Loeffen JLCM, Buskens CAF, Smeets RJP, Gozalbo MER, Budde SMS, Mariman EC, Wijburg FA, Barth PG, Trijbels JMF, Smeitink JAM. 1999. Leigh syndrome associated with a mutation in the NDUFS7 (PSST) nuclear encoded subunit of complex I. Ann Neurol 45: 787–790.
- Triepels RH, van den Heuvel LP, Trijbels JM, Smeitink JA. 2001. Respiratory chain complex I deficiency. Am J Med Genet, this issue.
- Valnot I, Osmond S, Gigarel N, Mehaye B, Amiel J, Cormier-Daire V, Munnich A, Bonnefont JP, Rustin P, Rotig A. 2000a. Mutations of the SOC1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy. Am J Hum Genet 67: 1104–1109.
- Valnot I, von Kleist-Retzow JC, Barrientos A, Gorbatyuk M, Taanman JW, Mehaye B, Rustin P, Tzagoloff A, Munnich A, Rotig A. 2000b. A mutation in the human heme A:farnesyltransferase gene (COX10 ) causes cytochrome c oxidase deficiency. Hum Mol Genet 9: 1245–1249.
- van den Heuvel L, Ruitenbeek W, Smeets R, Gelman-Kohan Z, Elpeleg O, Loeffen J, Trijbels F, Mariman E, de Bruijn D, Smeitink J. 1998. Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit. Am J Hum Genet 162: 262–268.
- Velier J, Kim M, Schwarz C, Kim TW, Sapp E, Chase K, Aronin N, DiFiglia M. 1998. Wild-type and mutant huntingtins function in vesicle trafficking in the secretory and endocytic pathways. Exp Neurol 152: 34–40.
- Wallace DC, Stugard C, Murdock D, Schurr T, Brown MD. 1997. Ancient mtDNA sequences in the human nuclear genome: a potential source of errors in identifying pathogenic mutations. Proc Natl Acad Sci U S A 94: 14900–14905.
- Webb S, Flanagan N, Callaghan N, Hutchinson M. 1997. A family with hereditary spastic paraparesis and epilepsy. Epilepsia 38: 495–499.
- Wong PC, Pardo CA, Borchelt DR, Lee MK, Copeland NG, Jenkins NA, Sisodia SS, Cleveland DW, Price DL. 1995. An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron 14: 1105–1116.
- Wong-Riley MTT. 1989. Cytochrome oxidase: an endogenous metabolic marker for neuronal activity. Trends Neurosci 12: 94–101.
- Zhu Z, Yao J, Johns T, Fu K, De BieI, Macmillan C, Cuthbert AP, Newbol RF, Wang J, Chevrette M, Brown GK, Brown RM, Shoubridge EA. 1998. SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome. Nature Genet 20: 328–343.