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Expert Opinion on Biological Therapy Volume 1, 2001 - Issue 5
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Review

Development of lipophilic cations as therapies for disorders due to mitochondrial dysfunction

Michael P Murphy MRC-Dunn Human Nutrition Unit, Wellcome Trust-MRC Building, Hills Road, Cambridge CB2 2XY, UK. [email protected]
Pages 753-764 | Published online: 23 Feb 2005

Bibliography

  • NICHOLLS DG, FERGUSON SJ: Bioenergetics 2 Academic Press, London (1992).
  • •The standard textbook on mitochondria' bioenergetics.
  • TYLER D: The Mitochondrion in Health and Disease. VCH, New York (1992).
  • •An introduction to mitochondria' biology.
  • SCHEFFLER IE: Mitochondria. Wiley-Liss, New York (1999).
  • •An excellent introduction to all aspects of mitochondria.
  • Mitochondria: DNA, proteins and disease. Darley-Usmer V, Schapira AHV (Eds.) Portland Press, London (1994).
  • ERNSTER L, LUFT R. ORRENIUS S: Mitochondrial diseases. Biochlin. Biophys. Acta (1995) 1271:1–292.
  • •An issue devoted to mitochondrial diseases.
  • SCHON EA: Mitochondrial genetics and disease. TIBS (2000) 25:555–560.
  • •A good review of mtDNA diseases.
  • NICOTERAP, BELLOMO G, ORRENIUS S: Calcium-mediated mechanisms in chemically induced cell death. Ann. Rev Phannacol. Toxicol. (1992) 32:449–470.
  • BOSS 0, MUZZIN P, GIACOBINO J-P: The uncoupling proteins, a review. Euro. Endocrinol. (1998) 139:1–9.
  • GREEN DR, REED JC: Mitochondria and apoptosis. Science (1998) 281:1309–1312.
  • NICHOLLS DG, BUDD SL: Mitochondria and neuronal survival. Physiol. Rev (2000) 80:316–360.
  • NISHIKAWA T, EDELSTEIN D, DU XL et al.: Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature (2000) 404:787–790.
  • LUFT R, IKKOS D, PALMIERI G, ALE: A case of severe hypermetabolism of nonthyroid origin with a defect in the maintenance of mitochondrial respiratory chain control. A correlated clinical, biochemical and morphological study. an. Invest. (1962) 41:1776–.
  • LUFT R: The development of mitochondrialmedicine. Proc. Nati Acad. Sci. USA (1994) 91:8731–8738.
  • SMEITINK J, VAN DEN HEUVEL L, DIMAURO S: The genetics and pathology of oxidative phosphorylation. Nature Rev Genet. (2001) 2:342–352.
  • ••An excellent review of mitochondria'diseases.
  • SCHOLTE HR: The biochemical basis of mitochondrial diseases. j Bioenerget. Biornembr. (1988) 20:161–191.
  • CHINNERY PE AL E: Epidemiology of pathogenic mitochondrial DNA diseases. Ann. Neural. (2000) 48:188–193.
  • LEONARD JV, SCHAPIRA AH: Mitochondrial respiratory chain disorders I: mitochondrial DNA defects. Lancet (2000) 355:299–304.
  • WALLACE DC: Mitochondrial diseases in man and mouse. Science (1999) 283:1482–1488.
  • ATTIMONELLI M, ALTAMURA N, BENNE R etal.: MitBASE : a comprehensive and integrated mitochondrial DNA database. The present status. Nucleic Adds Res. (2000) 28:148–152.
  • ANDERSON S, BANKIER AT, BARRELL BG etal.: Sequence and organization of the human mitochondrial genome. Nature (1981) 290:457–465.
  • •A classic paper reporting the human mitochondria' DNA sequence.
  • HOLT IJ, HARDING AE, MORGAN-HUGHES JA: Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature (1988) 331:717–719.
  • •The first reports (along with [22]) of a pathogenic mtDNA mutation.
  • WALLACE DC, SINGH G, LOTT MT et al.: Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science (1988) 242:1427–1430.
  • •The first reports (along with [21]) of a pathogenic mtDNA mutation.
  • CHINNERY PF, TURNBULL DM: Mitochondrial medicine. Q. j Med. (1997) 90:657–667.
  • ••An excellent review of mitochondria'medicine.
  • CHINNERY PF, TURNBULL DM: Mitochondrial DNA mutations in the pathogenesis of human disease. Mol. Med. Today (2000) 6:425-432.ccA review covering all aspects of mtDNAdiseases.
  • ETO K, TSUBAMOTO Y, TERAUCHI Y et al.: Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion. Nature 759 (1999) 283:981–985.
  • FISCHEL-GHODSIAN N: Mitochondrial DNA mutations and diabetes: another step toward individualized medicine. Ann. Intern. Med. (2001) 134:777–779.
  • REID FM, VERNHAM GA, JACOBS HT: A novel mitochondrial point mutation in a maternal pedigree with sensorineural deafness. Human Mut. (1994) 3:243–247.
  • RIORDAN-EVA P, HARDING AE: Leber's hereditary optic neuropathy: the clinical relevance of different mitochondrial DNA mutations. j Med. Genet. (1995) 32:81–87.
  • TAYLOR RW, CHINNERY PF, TURNBULL DM, LIGHTOWLERS RN: Selective inhibition of mutant human mitochondrial DNA replication in vitro by peptide nucleotide acids. Nature Genet. (1997) 15:212–215.
  • ROSSIGNOL R, MALGAT M, MAZAT J-P, LETELLIER T: Threshold effect and tissue specificity. Implication for mitochondrial cytopathies. j Biol. Chem. (1999) 274:33426–33432.
  • WALLACE DC: Mitochondrial DNA variation in human evolution, degenerative disease and aging. Am. I Hum. Genet. (1995) 57:201–223.
  • RICHTER C, PARK J-W, AMES BN: Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc. Natl. Acad. Sri. USA (1988) 85:6465–6467.
  • •The first report that mtDNA is more oxidatively damaged than nuclear DNA.
  • LARSSON N-G, CLAYTON DA: Molecular genetic aspects of human mitochondrial disorders. Anna Rev. Genet. (1995) 29:151–178.
  • MICHIKAWA Y, MAZZUCCHELLI BRESOLIN N, SCARLATO G, ATTARDI G: Aging-dependent large accumulation of point mutations in the human mtDNA control region for replication. Science (1999) 286:774–779.
  • •An important study that showed the accumulation of mitochondrial DNA mutations with age, although the functional consequences of the mtDNA mutations were uncertain.
  • CORRAL-DEBRINSKI M, HORTON T, LOTT MT, SHOFFNER JM, BEAL MF, WALLACE DC: Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age. Nature Genet. (1992) 2:324–329.
  • PITKANEN S, ROBINSON BH: Mitochondria' complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase. OM. Invest. (1996) 98:345–351.
  • •A demonstration that mtDNA mutations may lead to increased mitochondrial radical production.
  • PORTEOUS WK, JAMES AM, SHEARD PW et al.: Bioenergetic consequences of accumulating the common 4,977 bp mitochondrial DNA deletion. Eur. Biochem. (1998) 257:192–201.
  • LINNANE AW, MARZUKI S, OZAWA T, TANAKA M: Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet (1989) 1:642–645.
  • ELSON JL, SAMUELS DC, TURNBULL DM, CHINNERY PF: Random intracellular drift explains the clonal expansion of mitochondrial DNA mutations with age. Am. I Hum. Genet. (2001) 68:802–806.
  • ATTARDI G: Biogenesis of mitochondria.Ann. Rev Cell. Biol. (1988) 4:289–333.
  • SCHATZ G: The protein import system of mitochondria. j Biol. Chem. (1996) 271:31763–31766.
  • KOEHLER CM, LEUENBERGER D, MERCHANT S, RENOLD A, JUNNE T, SCHATZ G: Human deafness dystonia syndrome is a mitochondrial disease. Proc. Natl. Acad. Sri. USA (1999) 96:2141–2146.
  • •The first mitochondrial disease due to a defect in mitochondrial protein import.
  • BOURGERON T, AL E: Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nature Genet. (1995) 11:144–149.
  • •A mitochondrial disease due to a nuclear mutation in a respiratory chain protein.
  • KAUKONEN J, JUSELIUS JK, TIRANTI V et al.: Role of adenine nucleotide translocator in mtDNA maintenance. Science (2000) 289:782–785.
  • PRZYREMBEL H: Therapy of mitochondrial disorders. j Inherit. Metab. Dis. (1987) 10:129–146.
  • •An early review of therapies for mitochondrial disorders, before diseases due to mtDNA mutations were known.
  • LEONARD JV, SCHAPIRA AH: Mitochondrial respiratory chain disorders II: neurodegenerative disorders and nuclear gene defects. Lancet (2000) 355:389–394.
  • ••A review focusing on the role of mitochondrial dysfunction in neurodegenerative diseases.
  • CAMPUZANO V, MONTERMINI L, MOLTO MD et al.: Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science (1996) 271:1423–1427.
  • KAPLAN J: Friedreich's ataxia is a mitochondrial disorder. Proc. Natl. Acad. Li. USA (1999) 96:10948–10949.
  • •A good review of Friedreich's ataxia.
  • PUCCIO H, KOENIG M: Recent advances in the molecular pathogenesis of Friedreich ataxia. Human Malec. Genet. (2000) 9:887–892.
  • PUCCIO H, SIMON D, COSSEE M et al.: Mouse models for Friedreich ataxia exhibit cardiomopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits. Nature Genetics (2001) 27:181–186.
  • ••An important paper reporting thedevelopment of conditional frataxin 'knockout' mice whose pathology strongly suggests mitochondrial oxidative damage as the primary pathological event in the disease.
  • KOUTNIKOVA H, CAMPUZANO V, FOURY E DOLLE P, CAZZALINI 0, KOENIG M: Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin. Nature Genet. (1997) 16:345–351.
  • LODI R, COOPER JM, BRADLEY JL et al.: Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia. Proc. Nati Acad. Sri USA (1999) 96:11492–11495.
  • ••An important paper directly measuring amitochondrial defect in Freidreich's ataxia patients by 31P-NMR. This suggests how future measurements of efficacy of therapies for mitochondrial diseases can be made.
  • CAVALIER L, OUAHCHI K, KAYDEN HJ et al.: Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families. Am. j Hum. Genet. (1998) 62:301–310.
  • EMOND M, LEPAGE G, VANASSE M, PANDOLFO M: Increased levels of plasma malondialdehyde in Friedreich ataxia. Neurology (2000) 55:1752–1753.
  • SCHULZ JB, DEHMER T, SCHOLS L et al.: Oxidative stress in patients with Friedreich ataxia. Neurology (2000) 55:1719–1721.
  • SOKOL RJ, TWEDT D, MCKIM JM Jr. et al.: Oxidant injury to hepatic mitochondria in patients with Wilson's disease and Bedlington terriers with copper toxicosis. Gastroenterology (1994) 107:1788–1798.
  • LUTSENKO S, COOPER MJ: Localization of the Wilson's disease protein product to mitochondria. Proc Natl. Acad. Sci. USA (1998) 95:6004–6009.
  • GUM, COOPER JM, BUTLER P et al:Oxidative-phosphorylation defects in liver of patients with Wilson's disease. Lancet (2000) 356:469–474.
  • BOVERIS A and CADENAS E: Mitochondrial production of superoxide anions and its relationship to the antimycin insensitive respiration. FEBS Lett. (1975) 54:311–314.
  • BECKMAN KB, AMES BN: The free radical theory of aging matures. Phys. Rev (1998) 78:547–581.
  • •A survey of the role of mitochondrial oxidative damage in degenerative diseases and ageing.
  • RAHA S, ROBINSON BH: Mitochondria, oxygen free radicals, disease and ageing. Trends Biachein. (2000) 25:502–508.
  • •A review of mitochondrial free radical production.
  • RADI R, RODRIGUEZ M, CASTRO L, TELLERI R: Inhibition of mitochondrial electron transport by peroxynitrite. Arch. Biachein. Biophys. (1994) 308:89–95.
  • GEROMEL V, KADHOM N, CEBALOS-PICOT I etal.: Superoxide-induced massive apoptosis in cultured skin fibroblasts harboring the neurogenic ataxia retinitis pigmentosa (NARP) mutation in the ATPase-6 gene of the mitochondrial DNA. Hum. Mal Genet. (2001) 10:1221–1228.
  • CHANCE B, SIES H, BOVERIS A: Hydroperoxide metabolism in mammalian organs. Physial. Rev (1979) 59:527–605.
  • ••One of the first detailed studies onmitochondrial radical production.
  • BOVERIS A: Determination of the production of superoxide radicals and hydrogen peroxide in mitochondria. Methods Enzymol (1984) 105:429–435.
  • LI Y, HUANG T-T, CARLSON EJ et al: Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nature Genet. (1995) 11:376–381.
  • LEBOVITZ RM, ZHANG H, VOGEL H et al.: Neurodegeneration, myocardial injury and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proc. Natl. Acad. Li. USA (1996) 93:9782–9787.
  • REED D: Glutathione: toxicological implications. Ann. Rev Pharmacy]. Tarim]. (1990) 30:603–631.
  • COYLE JT, PUTTFARCKEN P: Oxidative stress, glutamate and neurodegenerative disorders. Science (1993) 262:689–694.
  • NICOTERA E ORRENIUS S: Ca2+ and cell death. Ann. NY Acad. Sci (1992) 648:17–27.
  • SCHAPIRA AHV, COOPER JM, DEXTER D, CLARK JB, JENER E MARSDEN CD: Mitochondrial complex 1 deficiency in Parkinson's disease. Neurochem. (1990) 54:823–827.
  • COOPER JM, MANN VM, KRIGE D, SCHAPIRA AHV: Human mitochondrial complex 1 dysfunction. Biochimica et Biophysica Acta (1992) 1101:198–203.
  • •A review of complex I damage in Parkinson's disease.
  • JENNER P: Altered mitochondrial function, iron metabolism and glutathione levels in Parkinson's disease. Acta Neural Scam/. Suppl. (1993) 146:6–13.
  • LODI R, SCHAPIRA AH, MANNERS D et al.: Abnormal in vivo skeletal muscle energy metabolism in Huntington's disease and dentatorubropallidoluysian atrophy. Ann. Neural (2000) 48:72–76.
  • TABRIZI SJ, WORKMAN J, HART PE et al.: Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse. Ann. Neural (2000) 47:80–86.
  • SHIGENAGA MK, HAGEN TM, AMES BN: Oxidative damage and mitochondrial decay in aging. Proc. Natl. Acad. Sci. USA (1994) 91:19771–19778.
  • BEAL MF: Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? Ann. Neural. (1992) 31:119–130.
  • PRICE DL, SISODIA SS, BORCHELT DR: Genetic neurodegenerative diseases: the human illness and transgenic models. Science (1998) 282:1079–1083.
  • SHOULSON I: Experimental therapeutics of neurodegenerative disorders: unmet needs. Science (1998) 282:1072–1074.
  • FINKEL T, HOLBROOK NJ: Oxidants, oxidative stress and the biology of ageing. Nature (2000) 408:239–247.
  • •A good starting point for the role of oxidative damage in ageing.
  • MORGAN-HUGHES JA: Mitochondria' diseases. In: Myology.2). Engel AG, Franzini-Armsrong C (Eds.), Volume 2 (1992):1610–1660.
  • WALKER UA, BYRNE E: The therapy of respiratory chain encephalomyopathy: a critical review of the past and current perspective. Acta Neural Land. (1995) 92:273–280.
  • DIMAURO S, HIRANO M, SCHON EA: Mitochondrial encephalomyopathies: therapeutic approaches. Neural Sci. (2000) 21:S901–908.
  • SCHAPIRA AH: Mitochondrial disorders. Cun: Opin. Neural (2000) 13:527–532.
  • •A clinically-oriented review of mitochondrial disorders.
  • TAYLOR RW, CHINNERY PF, CLARK KM, LIGHTOWLERS RN, TURNBULL DM: Treatment of mitochondrial disease. Bioenerg. Biomembr (1997) 29:195–205.
  • •An excellent survey of therapies used to date for mitochondrial medicine.
  • VLADUTIU GD: Advances in the genetic mechanisms of mitochondrial disease. Curr. Opin Neural. (1997) 10:512–518.
  • WALKER UA, COLLINS S, BYRNE E: Respiratory chain encephalomyopathies: a diagnostic classification. Eur. Neural (1996) 36:260–267.
  • VAN BEEKVELT MC, VAN ENGELEN BG, WEVERS RA, COLIER WN: Quantitative near-infrared spectroscopy discriminates between mitochondrial myopathies and normal muscle. Ann. Neural (1999) 46:667–670.
  • CHINNERY PF, TURNBULL DM: Clinical features, investigation and management of patients with defects of mitochondrial DNA. I Neural Neurosurg. Psychiatry (1997) 63:559–563.
  • TARNOPOLSKY MA, ROY BD, MACDONALD JR: A randomized, controlled trial of creatine monohydrate in patients with mitochondrial cytopathies. Muscle Nerve (1997) 20:1502–1509.
  • KLOPSTOCK T, QUERNER V, SCHMIDT F, GEKELER F et al: A placebo-controlled crossover trial of creatine in mitochondrial diseases. Neurology (2000) 55:1748–1751.
  • HARPEY JP, CHARPENTIER C, COUDE M: Methylene-blue for riboflavin-unresponsive glutaricaciduria Type II. Lancet (1986) 1:391.
  • ELEFF S, KENNAWAY NG, BUIST NR et al.: 3113 NMR study of improvement in oxidative phosphorylation by vitamins K3 and C in a patient with a defect in electron transport at complex III in skeletal muscle. Proc. Natl. Acad. Sci. USA (1984) 81:3529–3533.
  • •One of the first attempts at a rational therapy for mitochondrial diseases.
  • SCHOLTE HR, BUSCH HFM, BAKKER HD, BOGAARD JM, LUYT-HOUWEN IEM, KUYT LP: Riboflavin-responsive complex I deficiency. Biochim. Biophys. Acta (1995) 1271:75–83.
  • HAGEN TM, WEHR CM, AMES BN: Mitochondrial decay in aging. Ann. NY Acad. Sci. (1998) 854:215–223.
  • HAGEN TM, AL E: Mitochondrial decay in hepatocytes from old rats. Proc. Natl. Acad. Sci. USA (1997) 94:3064–3069.
  • DE STEFANO N, MATTHEWS PM, FORD B, GENGE A, KARPATI G, ARNOLD DL: Short-term dichloroacetate treatment improves indices of cerebral metabolism in patients with mitochondrial disorders. Neurology (1995) 45:1193–1198.
  • SUH JH, SHIGENO ET, MORROW JD et al.: Oxidative stress in the aging rat heart is reversed by dietary supplementation with (R)-(alpha)-lipoic acid. FASEB J. (2001) 15:700–706.
  • HAGEN TM, INGERSOLL RT, LYKKESFELDT J et al.: (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage and increased metabolic rate. FASEB J. (1999) 13:411–418.
  • MIQUEL J, FERRANIZ ML, DE JUAN E, SEVILLA I, MARTINEZ M: N-acetylcysteine protects against age-related decline of oxidative phosphorylation in liver mitochondria. Eur. j Pharmacy]. (1995) 292:333–335.
  • MELOV S, SCHNEIDER JA, DAY BJ et al.: A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase. Nature Genet. (1998) 18:159–163.
  • SALVEMINI D, WANG Z-Q, ZWEIER JL etal.: A nonpeptidyl mimic of superoxide dismutase with therapeutic activity in rats. Science (1999) 286:304–306.
  • RONG Y, DOCTROW SR, TOCCO G, BAUDRY M: EUK-134, a synthetic superoxide dismutase and catalase mimetic, prevents oxidative stress and attenuates kainate-induced neuropathology. Proc. Natl. Acad. Sci. USA (1999) 96:9897–9902.
  • BUTTERFIELD DA, HOWARD BJ, YATIN S, ALLEN KL, CARNEY JM: Free radical oxidation of brain proteins in accelerated senesence and its modulation by N-tert-butyl-alpha-phenylnitrone. Proc. Natl Acad. Sci. USA (1997) 94:674–678.
  • SOKOL RJ, MCKIM JM, GOFF MC et al.: Vitamin E reduces oxidant injury to mitochondria and the hepatoxicity of taurochenodeoxycholic acid in the rat. Gastroenterology (1998) 114:164–174.
  • CRANE FL, BARR R: Determination of ubiquinones. Meth. Enzyme]. (1971) 18C:137–165.
  • CRANE FL: Hydroquinone dehydrogenases. Ann. Rev. Biachern. (1977) 46:439–469.
  • ERNSTER L, DALLNER G: Biochemical, physiological and medical aspects of ubiquinone function. Biochim. Biophys. Acta (1995) 1271:195–204.
  • INGOLD KU, BOWRY VW, STOCKER R, WALLING C: Autoxidation of lipids and antioxidation by a-tocopherol and ubiquinol in homogeneous solution and in aqueous dispersions of lipids. Proc. Nati Acad. Sci. USA (1993) 90:45–49.
  • MAGUIRE JJ, WILSON DS, PACKER L: Mitochondrial electron transport-linked tocopheroxyl radical reduction. I Biol. Chem. (1989) 264:21462–21465.
  • STOYANOVSKY DA, OSIPOV AN, QUINN PJ, KAGAN VE: Ubiquinone-dependent recycling of vitamin E radicals by superoxide. Arch. Biochem. Biophys. (1995) 323:343–351.
  • ROTIG A, APPELKVIST EL, GEROMEL V et al.: Quinone-responsive multiple respiratory-chain dysfunction due to widespread coenzyme Q10 deficiency. Lancet (2000) 356:391–395.
  • •One of the few cases, along with [113], where a simple therapy for a mitochondrial disease works.
  • MUSUMECI 0, NAINI A, SLONIM AE etal.: Familial cerebellar ataxia with muscle coenzyme Q10 deficiency. Neurology (2001) 56:849–855.
  • •One of the few cases, along with [112], where a simple therapy for a mitochondrial disease works.
  • YUZURIHA T, TAKADA M, KATAYAMA K: Transport of [14Clcoenzyme Q10 from the liver to other tissues after intravenous administration to guinea pigs. Biochim. Biophys. Acta (1983) 759:286–291.
  • MATTHEWS RT, YANG L, BROWNE S, BAIL M, BEAL MF: Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neurprotective effects. Proc. Natl. Acad. Sci. USA (1998) 95:8892–8897.
  • ROSENFELDT FL, PEPE S, OUR et al.: Coenzyme Q10 improves the tolerance of the senescent myocardium to aerobic and ischemic stress: studies in rats and in human atrial tissue. Biefactors (1999) 9:291–299.
  • SHOFFNER JM, LOTT MT, VOLJAVEC AS etal.: Spontaneous Kearns-Sayre/chronic external ophthalmoplegia plus syndrome associated with a mitochondrial DNA deletion: a slip replication model and metabolic therapy. Proc. Natl. Acad. Li. USA (1989) 86:7952–7956.
  • BRESOLIN N, DORIGUZZI C, PONZETTO C et al.: Ubidecarenone in the treatment of mitochondrial myopathies: a multi-center double-blind trial. ..J. Neural. Li. (1990) 100:70–78.
  • MATTHEWS PM, FORD B, DANDURAND RJ et al.: Coenzyme Q10 with multiple vitamins is generally ineffective in treatment of mitochondrial disease. Neurology (1993) 43:884–890.
  • PETERSON PL: The treatment of mitochondrial myopathies and encephalomyopathies. Biochim. Biophys. Acta (1995) 1271:275–280.
  • GOLD R, SEIBEL P, REINELT G et al.: Phosphorus magnetic resonance spectroscopy in the evaluation of mitochondrial myopathies: results of a 6-month therapy study with coenzyme Q. Eur. Neural. (1996) 36:191–196.
  • OZAWA T: Genetic and functional changes in mitochondria associated with aging. Physial. Rev (1997) 77:425–464.
  • YU CA, YU L: Syntheses of biologically active ubiquinone derivatives. Biochemistry (1982) 21:4096–4101.
  • GILLIS JC, BENEFIELD P, MCTAVISH D: Idebenone. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in age-related cognitive disorders. Drugs Aging (1994) 5:133–152.
  • •A review of one of the most promising anti-oxidants commonly given to mitochondrial patients.
  • IMADA I, FUJITA T, SUGIYAMA Y, OKAMOTO K, KOBAYASHI Y: Effects of idebenone and related compounds on respiratory activities of brain mitochondria and on lipid peroxidation of their membranes. Arch. Cerantal. Ceriatr. (1989) 8:323–341.
  • TORII H, YOSHIDA K, KOBAYASHI T, TSUKAMOTO T, TANAYAMA S: Disposition of idebenone (CV-2619), a new cerebral metabolism improving agent, in rats and dogs. I Pharmacobiodyn. (1985) 8:457–467.
  • LODI R, HART PE, RAJAGOPALAN Bet al.: Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in patients with Friedreich's ataxia. Ann. Neural. (2001) 49:590–596.
  • RUSTIN P, VON KLEIST-RETZOW JC, CHANTREL-GROUSSARD K etal.: Effect of idebenone on cardiomyopathy in Friedreich's ataxia: a preliminary study. Lancet (1999) 354:477–479.
  • LERMAN-SAGIE T, RUSTIN P, LEV D et al.: Dramatic improvement in mitochondrial cardiomyopathy following treatment with idebenone. j Inherit. Metab. Dis. (2001) 24:28–34.
  • NAPOLITANO A, SALVETTI S, VISTA M et al.: Long-term treatment with idebenone and riboflavin in a patient with MELAS. Neural. Li. (2000) 21:S981–982.
  • WEYER G, BABEJ-DOLLE RIVI, HADLER D, HOFMANN S and HERRMANN WM: A controlled study of 2 doses of idebenone in the treatment of Alzheimer's disease. Neuropsychabialogy (1997) 36:73–82.
  • MUELLER GM, MCKENZIE LR, HOMANIACS GE, WATKINS SC, ROBBINS PD, PAUL HS: Complementation of defective leucine decarboxylation in fibroblasts from a maple syrup urine disease patient by retrovirus-mediated gene transfer. Gene Therapy (1995) 2:461–468.
  • CHRZANOWSKA-LIGHTOWLERS ZMA, LIGHTOWLERS RN, TURNBULL DM: Gene therapy for mitochondrial DNA defects: is it possible? Gene Therapy (1995) 2:311–316.
  • •A review outlining the difficulties facing mtDNA gene therapies.
  • MURPHY MP: Targeting bioactive compounds to mitochondria. Trends Biatechrial (1997) 15:326–330.
  • •An outline of the strategies that can be used to target molecules to mitochondria.
  • COLLOMBET JM, COUTELLE C: Towards gene therapy of mitochondrial disorders. Mal Med. Today (1998) 4:31–38.
  • KOLESNIKOVA OA, ENTELIS NS, MIREAU H, FOX TD, MARTIN TD, TARASSOV IA: Suppression of mutations in mitochondrial DNA by tRNAs imported from the cytoplasm. Science (2000) 289:1931–1933.
  • CLARK K, AL E: Correction of a mitocohondrial DNA defect in human skeletal muscle. Nature Genet. (1997) 16:222–224.
  • TAIVASSALO T, FU K, JOHNS T, ARNOLD D, KARPATI G, SHOUBRIDGE EA: Gene shifting: a novel therapy for mitochondrial myopathy. Hum. Mal Cenci. (1999) 8:1047–1052.
  • RUBENSTEIN DS, THOMASMA DC, SCHON EA, ZINAMAN MJ: Germ-line therapy to cure mitochondrial disease: protocol and ethics of in vitro ovum nuclear transplantation. Camb. Q Healthc. Ethics (1995) 4:316–339.
  • SOHOL RS, WEINDRUCH R: Oxidative stress, caloric restriction and aging. Science (1996) 273:59–63.
  • LEE C-K, KLOPP RG, WEINDRUCH R, PROLLA TA: Gene expression profile of aging and its retardation by caloric restriction. Science (1999) 285:1390–1393.
  • MURPHY MP, SMITH RAJ: Drug delivery to mitochondria: the key to mitochondrial medicine. Advanced Drug Deity Rev (2000) 41:235–250.
  • CHEN LB: Mitochondrial membrane potential in living cells. Ann. Rev Cell Biol. (1988) 4:155–181.
  • LIBERMAN EA, TOPALI VP, TSOFINA LM, JASAITIS AA, SKULACHEV VP: Mechanism of coupling of oxidative phosphorylation and the membrane potential of mitochondria. Nature (1969) 222:1076–1078.
  • ••The first demonstration of the uptake oflipophilic phosphonium cations by mitochondria.
  • AZZONE GE PIETROBON D, ZORATTI M: Determination of the proton electrochemical gradient across biological membranes. Curr. Topics Biaeriergetics (1984) 13:1–77.
  • BRAND MD: Measurement of mitochondrial protonmotive force. In: Biaeriergetics - a practical approach. GC Brown, CE Cooper (Eds.), IRL, Oxford (1995):39–62.
  • RIDEOUT DC, CALOGEROPOULOU T, JAWORSKI JS, DAGNINO R, MCCARTHY MR: Phosphonium salts exhibiting selective anti-carcinoma activity in vitro. Anti-Cancer Drug Design (1989) 4:265–280.
  • RIDEOUT D: Self assembling drugs: anew approach to biochemical modulation in cancer chemotherapy. Cancer Invest. (1994) 12:189–202.
  • RIDEOUT D, BUSTAMANTE A, PATEL J: Mechanism of inhibition of FaDu hypopharyngeal carcinoma cell growth by tetraphenylphosphnium chloride. Int. Cancer (1994) 57:247–253.
  • MODICA-NAPOLITANO JS, APRILLE JR: Delocalized lipophilic cations selectively target the mitochondria of carcinoma cells. Adv. Drug Deify. Rev (2001) 49:63–70.
  • BURNS RJ, SMITH RAJ, MURPHY MP: Synthesis and characterization of thiobutyltriphenylphosphonium bromide, a novel thiol reagent targetted to the mitochondrial matrix. Arch. Biochem. Biophys. (1995) 322:60–68.
  • BURNS RJ, MURPHY MP: Labelling of mitochondrial proteins in living cells by the thiol probe thiobutyltriphenylphosphonium bromide. Arch. Biochem. Biophys. (1997) 339:33–39.
  • SMITH RAJ, PORTEOUS CM, COULTER CV, MURPHY MP: Targeting an antioxidant to mitochondria. Eur. Biochem. (1999) 263:709–716.
  • •The first demonstration that anti-oxidants could be targeted to mitochondria within cells.
  • COULTER CV, KELSO GF, LIN T-K, SMITH RAJ, MURPHY MP: Mitochondrially targeted antioxidants and thiol reagents. Free Rad. Biel Med. (2000) 28:1547–1554.
  • KELSO GF, PORTEOUS CM, COULTER CV etal.: Selective targeting of a redox-active ubiquinone to mitochondria within cells. I Biel Chem. (2001) 276:4588–4596.
  • ••A demonstration that a ubiquinol analoguecan be targeted to mitochondria within cells where it acts as an anti-oxidant and can be recycled by the respiratory chain.
  • MURATOVSKA A, LIGHTOWLERS RN, TAYLOR RW et al: Targeting peptide nucleic acid (PNA) oligomers to mitochondria within cells by conjugation to lipophilic cations: implications for mitochondrial DNA replication, expression and disease. Nucleic Acids Res. (2001) 29:1852–1863.
  • KAUPPINEN R: Proton electrochemical potential of the inner mitochondrial membrane in isolated perfused rat hearts, as 153 measured by exogenous probes. Biochim. Biophys. Acta (1983) 725:131–137.
  • SRIVASTAVA PC, HAY HG, KNAPP FF: Effects of alkyl and aryl substitution on the myocardial specificity of radioiodinated phosphonium, arsonium and ammonium cations. j Med. Chem. (1985) 28:901–904.
  • FUKUDA H, SYROTA A, CHARBONNEAU P et al.: Use of 11C-triphenylmethylphosphonium for the evaluation of membrane potential in the heart by positron-emission tomography. Eur. J. Nucl. Med. (1986)11:478–483.
  • STEEN H, MARING JG, MEIJER DK: Differential effects of metabolic inhibitors on cellular and mitochondrial uptake of organic cations in rat liver. Biochem. Pharmacy]. (1993) 45:809–818.
  • WAN B, DOUMEN C, DUSZYNSKI J, SALAMA G, LANOUE KF: A method of determining electrical potential gradient across mitochondrial membrane in perfused rat hearts. Am. j Physiol. (1993) 265:H445–H452.
  • MITOMAP. http://infinity.gen.emory.edu/ mitomap.html

Website

  • •A useful website with information on all mtDNA diseases.

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