Skip to main content
SpringerLink
Log in

Mitochondrial DNA mutations in diseases of energy metabolism

  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

Abstract

A variety of degenerative diseases involving deficiencies in mitochondrial bioenergetics have been associated with mitochondrial DNA (mtDNA) mutations. Maternally inherited mtDNA nucleotide substitutions range from neutral polymorphisms to lethal mutations. Neutral polymorphisms are ancient, having accumulated along mtDNA lineages, and thus correlate with ethnic and geographic origin. Mildly deleterious base substitutions have also occurred along mtDNA lineages and have been associated with familial deafness and some cases of Alzheimer's Disease and Parkinson's Disease. Moderately deleterious nucleotide substitutions are more recent and cause maternally-inherited diseases such as Leber's Hereditary Optic Neuropathy (LHON) and Myoclonic Epilepsy and Ragged-Red Fiber Disease (MERRF). Severe nucleotide substitutions are generally new mutations that cause pediatric diseases such as Leigh's Syndrome and dystonia. MtDNA rearrangements also cause a variety of phenotypes. The milder rearrangements generally involve duplications and can cause maternally-inherited adult-onset diabetes and deafness. More severe rearrangements frequently involving detetions have been associated with adult-onset Chronic Progressive External Ophthalmoplegia (CPEO) and Kearns-Sayre Syndrome (KSS) or the lethal childhood disorder, Pearson's Marrow/Pancreas Syndrome. Defects in nuclear-cytoplasmic interaction have also been observed, and include an autosomal dominant mutation causing multiple muscle mtDNA deletions and a genetically complex disease resulting in the tissue depletion of mtDNAs. MtDNA nucleotide substitution and rearrangement mutations also accumulate with age in quiescent tissues. These somatic mutations appear to degrade cellular bioenergetic capacity, exacerbate inherited mitochondrial defects and contribute to tissue senescence. Thus, bioenergetic defects resulting from mtDNA mutations may be a common cause of human degenerative disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adams, V., Griffin, L., Towbin, J., Gelb, B., Worley, K., and McCabe, E. R. (1991). Porin interaction with hexokinase and glycerol kinase: metabolic microcompartmentation at the outer mitochondrial membrane,Biochem. Med. Metab. Biol. 45 271–291.

    Google Scholar 

  • Ballinger, S. W., Schurr, T. G., Torroni, A., Gan, Y. Y., Hodge, J. A., Hassan, K., Chen, K. H., and Wallace, D. C. (1992a). Southeast Asian mitochondrial DNA analysis reveals genetic continuity of ancient mongoloid migrations,Genetics 130 139–152.

    Google Scholar 

  • Ballinger, S. W., Shoffner, J. M., Hedaya, E. V., Trounce, I., Polak, M. A., Koontz, D. A., and Wallace, D. C. (1992b). Maternally transmitted diabetes and deafness associated with a 10.4-kb mitochondrial DNA deletion,Nature Genet. 1 11–15.

    Google Scholar 

  • Ballinger, S. W., Shoffner, J. M., Gebhart, S., Koontz, D. A., and Wallace, D. C. (1994). Mitochondrial diabetes and deafness: a complex mtDNA rearrangement results in failure of insulin production, in press.

  • Bandy, B., and Davison, A. J. (1990). Mitochondrial mutations may increase oxidative stress: implications for carcinogenesis and aging?Free Rad. Biol. Med. 8 523–539.

    Google Scholar 

  • Bindoff, L. A., Howell, N., Poulton, J., McCullough, D. A., Morten, K. J., Lightowlers, R. N., Turnbull, D. M., and Weber, K. (1993). Abnormal RNA processing associated with a novel tRNA mutation in mitochondrial DNA. A potential disease mechanism.J. Biol. Chem. 268 19559–19564.

    Google Scholar 

  • Brown, M. D., Voljavec, A. C., Lott, M. T., MacDonald, I., and Wallace, D. C. (1992a). Leber's hereditary optic neuropathy; a model for mitochondrial neurodegenerative diseases,FASEB J. 6 2791–2799.

    Google Scholar 

  • Brown, M. D., Voljavec, A. S., Lott, M. T., Torroni, A., Yang, C.-C., and Wallace, D. C. (1992b). Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy,Genetics 130 163–173.

    Google Scholar 

  • Cann, R. L., and Wilson, A. C. (1983). Length mutations in human mitochondrial DNA,Genetics 104 699–711.

    Google Scholar 

  • Cann, R. L., Stoneking, M., and Wilson, A. C. (1987). Mitochondrial DNA and human evolution,Nature (London) 325 31–36.

    Google Scholar 

  • Chung, A. B., Stepien, G., Haraguchi, Y., Li, K., and Wallace, D. C. (1993). Transcriptional control of nuclear genes for the mitochondrial muscle ADP/ATP translocator and the ATP synthase β subunit: multiple factors interact with the OXBOX/REBOX promoter sequences,J. Biol. Chem. 267 21154–21161.

    Google Scholar 

  • Cooper, J. M., Mannn, V. M., and Schapira, A. H. V. (1992). Analyses of mitochondrial respiratory chain function and mitochondrial DNA deletion in human skeletal muscle: effect of ageing,J. Neurol. Sci. 113 91–98.

    Google Scholar 

  • Corral-Debrinski, M., Stepien, G., Shoffner, J. M., Lott, M. T., Kanter, K., and Wallace, D. C. (1991). Hypoxemia is associated with mitochondrial DNA damage and gene induction,J. Am. Med. Assoc. 266 1812–1816.

    Google Scholar 

  • Corral-Debrinski, M., Horton, T., Lott, M. T., Shoffner, J. M., Beal, M. F., and Wallace, D. C. (1992a). Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age,Nature Genet. 2 324–329.

    Google Scholar 

  • Corral-Debrinski, M., Shoffner, J. M., Lott, M. T., and Wallace, D. C. (1992b). Association of mitochondrial DNA damage with aging and coronary atherosclerotic heart disease,Mutat. Res. 275 169–180.

    Google Scholar 

  • Cortopassi, G. A., and Arnheim, N. (1990). Detection of a specific mitochondrial DNA deletion in tissues of older humans,Nucleic Acids Res. 18 6927–6933.

    Google Scholar 

  • Cortopassi, G. A., Shibata, D., Soong, N.-W., and Arnheim, N. A. (1992). A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues,Proc. Natl. Acad. Sci. USA.89 7370–7374.

    Google Scholar 

  • Denaro, M., Blanc, H., Johnson, M. J., Chen, K. H., Wilmsen, E., Cavalli Sforza, L. L., and Wallace, D. C. (1981). Ethnic variation in Hpa 1 endonuclease cleavage patterns of human mitochondrial DNA,Proc. Natl. Acad. Sci. USA 78 5768–5772.

    Google Scholar 

  • DeVries, D. D., Van Engelen, B. G., Gabreels, F. J., Ruitenbeek, W., and Van Oost, B. A. (1993). A second missense mutation in the mitochondrial ATPase 6 gene in Leigh's syndrome,Ann. Neurol. 34 410–412.

    Google Scholar 

  • Dunbar, D. R., Moonie, P. A., Swingler, R. J., Davidson, D., Roberts, R., and Holt, I. J. (1993). Maternally transmitted partial direct tandem duplication of mitochondrial DNA associated with diabetes mellitus,Hum. Mol. Genet. 2 1619–1624.

    Google Scholar 

  • German, M. S. (1993). Glucose sensing in pancreatic islet beta cells: The key role of glucokinase and the glycolytic intermediates,Proc. Natl. Acad. Sci. USA 90 1781–1785.

    Google Scholar 

  • Gidh-Jain, M., Takeda, J., Xu, L. Z., Lange, A. J., Vionnet, N., Stoffel, M., Froguel, P., Velho, G., Sun, F., Cohen, D., Patel, P., Lo, Y. M. D., Hattersley, A. T., Luthman, H., Wedell, A., St. Charles, R., Harrison, R. W., Weber, I. T., Bell, G. I., and Pilkis, A. J. (1993). Glucokinase mutations associated with non-insulin-dependent (Type 2) diabetes mellitus have decreased enyzmatic activity: implications for structure/function relationships,Proc. Natl. Acad. Sci. USA 90 1932–1936.

    Google Scholar 

  • Giles, R. E., Blanc, H., Cann, H. M., and Wallace, D. C. (1980). Maternal inheritance of human mitochondrial DNA,Proc. Natl. Acad. Sci. USA.77 6715–6719.

    Google Scholar 

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

    Google Scholar 

  • Harman, D. (1972). The biologic clock: the mitochondria?J. Am. Ger. Soc. 20 145–147.

    Google Scholar 

  • Hayakawa, M., Hattori, H., Sugiyama, S., and Ozawa, T. (1992). Age-associated oxygen damage and mutations in mitochondrial DNA in human hearts,Biochem. Biophys. Res. Commun. 189 979–985.

    Google Scholar 

  • Hertzberg, M., Mickleson, K. N. P., Serjeantson, S. W., Prior, J. F., and Trent, R. J. (1989). An Asian specific 9-bp deletion of mitochondrial DNA is frequently found in Polynesians,Am. J. Hum. Genet. 44 504–510.

    Google Scholar 

  • Holt, I. J., Harding, A. E., and Morgan-Hughes, J. A. (1988). Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies,Nature (London) 331 717–719.

    Google Scholar 

  • Holt, I. J., Harding, A. E., Petty, R. K., and Morgan-Hughes, J. A. (1990). A new mitochondrial disease associated with mitochondrial DNA heteroplasmy,Am. J. Hum. Genet. 46 428–433.

    Google Scholar 

  • Howell, N., Bindoff, L. A., McCullough, D. A., Kubacka, I., Poulton, J., Mackey, D., Taylor, L., and Turnbull, D. M. (1991). Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees,Am. J. Hum. Genet. 49 939–950.

    Google Scholar 

  • Huoponen, K., Vilkki, J., Aula, P., Nikoskelainen, E. K., and Savontaus, M. L. (1991). A new mtDNA mutation associated with Leber hereditary optic neuroretinopathy,Am. J. Hum. Genet. 48 1147–1153.

    Google Scholar 

  • Huoponen, K., Lamminen, T., Juvonen, V., Aula, P., Nikoskelainen, E., and Savontaus, J. L. (1993). The spectrum of mitochondrial DNA mutations in families with Leber hereditary optic neuroretinopathy,Hum. Genet. 92 379–384.

    Google Scholar 

  • Johns, D. R., and Neufeld, M. J. (1991). Cytochromeb mutations in Leber hereditary optic neuropathy,Biochem. Biophys. Res. Commun. 181 1358.

    Google Scholar 

  • Johns, D. R., Neufeld, M. J., and Park, R. D. (1992a). An ND-6 mitochondrial DNA mutation associated with Lever hereditary optic neuropathy,Biochem. Biophys. Res. Commun. 187 1551–1557.

    Google Scholar 

  • Johns, D. R., Smith, K. H., and Miller, N. R. (1992b). Leber's hereditary optic neuropathy. Clinical manifestations of the 3460 mutation,Arch. Ophthalmol. 110 1577–1581.

    Google Scholar 

  • Johnson, M. J., Wallace, D. C., Ferris, S. D., Rattazzi, M. C., and Cavalli Sforza, L. L. (1983). Radiation of human mitochondria DNA types analyzed by restriction endonuclease cleavage patterns,J. Mol. Evol. 19 255–271.

    Google Scholar 

  • Jun, A. S., Brown, M. D., and Wallace, D. C. (1994). A Mitochondrial DNA mutation at np 14459 of the ND6 gene associated with maternally inherited Leber's hereditary optic neuropathy and dystonia,Proc. Nat. Acad. Sci. USA, in press.

  • Larsson, N. G., Holme, E., Kristiansson, B., Oldfors, A., and Tulinius, M. (1990). Progressive increase of the mutated mitochondrial DNA frcation in Kearns-Sayre syndrome,Pediatr. Res. 28 131–136.

    Google Scholar 

  • Linnane, A. W., Marzuki, S., Ozawa, T. and Tanaka, M. (1989). Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases,Lancet 1 642–645.

    Google Scholar 

  • Lott, M. T., Voljavec, A. S., and Wallace, D. C. (1990). Variable genotype of Lever's hereditary optic neuropathy patients,Am. J. Ophthalmol. 109 625–631.

    Google Scholar 

  • Mackey, D., and Howell, N. (1992). A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology,Am. J. Hum. Genet. 51 1218–1228.

    Google Scholar 

  • Malaisse-Lagae, F., and Malaisse, W. J. (1988). Hexose metabolism in pancreatic islets: regulation of mitochondrial hexokinase binding,Biochem. Med. Metab. Biol. 39 80–89.

    Google Scholar 

  • Merriwether, D. A., Clark, A. G., Ballinger, S. W., Schurr, T. G., Soodyall, H., Jenkins, T., Sherry, S. T., and Wallace, D. C. (1991). The structure of human mitochondrial DNA variation,J. Mol. Evol. 33 543–555.

    Google Scholar 

  • Miguel, J., Economos, A. C., Fleming, J., and Johnson, J. E. (1980). Mitochondrial role in cell aging,Exp. Gerontol. 15 575–591.

    Google Scholar 

  • Mita, S., Schmidt, B., Schon, E. A., DiMauro, S., and Bonilla, E. (1989). Detection of “deleted” mitochondrial genomes in cytochrome-c oxidase-deficient muscle fibers of a patient with Kearns-Sayre syndrome,Proc. Natl. Acad. Sci. USA 86 9509–9513.

    Google Scholar 

  • Moraes, C. T., DiMauro, S., Zeviani, M., Lombes, A., Shanske, S., Miranda, A. F., Nakase, H., Bonilla, E., Werneck, L. C., Servidei, S., Nonaka, I., Koga, Y., Spiro, A. J., Brownell, K. W., Schmidt, B., Schotland, D. L., Zupanc, M., DeVivo, D. C., Schon, E. A., and Rowland, L. P. (1989). Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome,N. Engl. J. Med. 320 1293–1299.

    Google Scholar 

  • Moraes, C. T., Shanske, S., Tritschler, H. J., Aprille, J. R., Andreetta, F., Bonilla, E., Schon, E. A., and DiMauro, S. (1991). MtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial disease,Am. J. Hum. Genet. 48 492–501.

    Google Scholar 

  • Moraes, C. T., Ciacci, F., Bonilla, E., Ionasescu, V., Schon, E. A., DiMauro, S. (1993). A mitochondrial tRNA anticodon swap associated with a muscle disease.Nat. Genet. 4 284–288.

    Google Scholar 

  • Munscher, C., Rieger, T., Muller-Hocker, J., and Kadenbach, B. (1993). The point mutation of mitochondrial DNA characteristic for MERRF disease is found also in healthy people of different ages,FEBS Lett. 317 27–30.

    Google Scholar 

  • Ortiz, R. G., Newman, N. J., Shoffner, J. M., Kaufman, A. E., Koontz, D. A., and Wallace, D. C. (1993). Variable retinal and neurologic manifestations in patients harboring the mitochondrial DNA 8993 mutation,Arch. Ophthalmol. 111 1525–1530.

    Google Scholar 

  • Otsuka, M., Niijima, K., Mizuno, Y., Yoshida, M., Kagawa, Y., and Ohta, S. (1990). Marked decrease of mitochondrial DNA with multiple deletions in a patient with familial mitochondrial myopathy,Biochem. Biophys. Res. Commun. 167 680–685.

    Google Scholar 

  • Poulton, J., Deadman, M. E., Bindoff, L., Morten, K., Land, J., and Brown, G. (1993). Families of mtDNA rearrangements can be detected in patients with mtDNA deletions: duplications may be a transient intermediate form,Hum. Mol. Genet. 2 23–30.

    Google Scholar 

  • Prezant, T. R., Agapian, J. V., Bohlman, M. C., Bu, X, Oztas, S., Qiu, W. Q., Arnos, K. S., Coropassi, G. A., Jaber, I., Rotter, J. I., Shohat, M., and Fischel-Ghodsian, N. (1993). Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and nonsyndromic deafness,Nature Genet. 4 289–294.

    Google Scholar 

  • Rötig, A., Colonna, M., Blanche, S., Fischer, A., LeDeist, F., Frezal, J., Saudubray, J. M., and Munnich, A. (1988). Deletion of blood mitochondrial DNA in pancytopenia,Lancet 2 567–568.

    Google Scholar 

  • Rötig, A., Colonna, M., Bonnefont, J. P., Blanche, S., Fischer, A., Saudubray, J. M., and Munnich, A. (1989). Mitochondrial DNA deletion in Pearson's marrow-pancreas syndrome,Lancet 1 902–903.

    Google Scholar 

  • Schurr, T. G., Ballinger, S. W., Gan. Y.-Y., Hodge, J. A., Merriwether, D. A., Lawrence, D. N., Knowler, W. C., Weiss, K. M., and Wallace, D. C. (1990). Amerindian mitochondrial DNAs have rare Asian mutations at high frequencies, suggesting they derived from four primary maternal lineages,Am. J. Hum. Genet. 46 613–623.

    Google Scholar 

  • Shoffner, J. M., Lott, M. T., Lezza, A. M., Seibel, P., Ballinger, S. W., and Wallace, D. C. (1990). Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNALys mutation,Cell 61 931–937.

    Google Scholar 

  • Shoffner, J. M., Fernhoff, M. D., Krawiecki, N. S., Caplan, D. B., Holt, P. J., Koontz, D. A., Takei, Y., Newman, N. J., Ortiz, R. G., Polak, M., Ballinger, S. W., Lott, M. T., and Wallace, D. C. (1992). Subacute necrotizing encephalopathy: oxidative phosphorylation defects and the ATPase 6 point mutation,Neurology 42 2168–2174.

    Google Scholar 

  • Shoffner, J. M., Brown, M. D., Torroni, A., Lott, M. T., Cabell, M. R., Mirra, S. S., Beal, M. F., Yang, C., Gearing, M., Salvo, R., Watts, R. L., Juncos, J. L., Hansen, L. A., Crain, B. J., Fayad, M., Reckord, C. L., and Wallace, D. C. (1993a). Mitochondrial DNA variants observed in Alzheimer disease and Parkinson disease patients,Genomics 17 171–184.

    Google Scholar 

  • Shoffner, J. M., Krawiecki, N., Cabell, M. F., Torroni, A., and Wallace, D. C. (1993b) A novel tRNALeu(UUR) mutation in childhood mitochondrial myopathy,Am. J. Hum. Genet. 53 (Suppl), No. 949.

  • Shoubridge, E. A., Karpati, G., and Hastings, K. E. M. (1990). Deletion mutants are functionally dominant over wild-type mitochondrial genomes in skeletal muscle fiber segments in mitochondrial disease,Cell 62 43–49.

    Google Scholar 

  • Simonetti, S., Chen, X., DiMauro, S., and Schon, E. A. (1992). Accumulation of deletions in human mitochondrial DNA during normal aging: analysis by quantitative PCR,Biochem. Biophys. Acta 1180 113–122.

    Google Scholar 

  • Singh, G., Lott, M. T., and Wallace, D. C. (1989). A mitochondrial DNA mutation as a cause of Leber's hereditary optic neuropathy,N. Engl. J. Med. 320 1300–1305.

    Google Scholar 

  • Soong, N. W., Hinton, D. R., Cortopassi, G., and Arnheim, N. (1992). Mosaicism for a specific somatic mitochondrial DNA mutation in adult human brain,Nature Genet. 2 318–323.

    Google Scholar 

  • Stoffel, M., Patel, P., Lo, Y. M., Hattersley, A. T., Lucassen, A. M., Page, R., Bell, J. I., Bell, G. I., and Turner, R. C. (1992). Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes,Nature Genet. 2 153–156.

    Google Scholar 

  • Stoneking, M., Jorde, L. B., Bhatia, K., and Wilson, A. C. (1990). Geographic variation in human mitochondrial DNA from Papua New Guinea,Genetics 124 717.

    Google Scholar 

  • Tatuch, Y., Christodoulou, J., Geigenbaum, A., Clarke, J. T. R., Wherret, J., Smith, C., Rudd, N., Petrova-Benedict, R., and Robinson, B. H. (1992). Heterplasmic mtDNA mutation (TG) at 8993 can cause Leigh disease when the percentage of abnormal mtDNA is high,Am. J. Hum. Genet. 50 852–858.

    Google Scholar 

  • Tritschler, H.-J., Andreetta, F., Moraes, C. T., Bonilla, E., Arnaudo, E., Danon, M. J., Glass, S., Zelaya, B. M., Vamos, E., Telerman-Toppet, N., Shanske, S., Kadenback, B., DiMauro, S., and Schon, E. A. (1992). Mitochondrial myopathy of childhood associated with depletion of mitochondrial DNA,Neurology 42 209–217.

    Google Scholar 

  • Torroni, A., Schurr, T. G., Yang, C.-C., Szathmary, E. J., Williams, R. C., Schanfield, M. S., Troup, G. A., Knowler, W. C., Lawrence, D. N., and Weiss, K. M. (1992). Native American mitochondrial DNA analysis indicates that the Amerind and the Nadene populations were founded by two independent migrations,Genetics 130 153–162.

    Google Scholar 

  • Torroni, A., Schurr, T. G., Cabell, M. F., Brown, M. D., Neel, J. V., Larsen, M., Smith, D. G., Vullo, C. M., and Wallace, D. C. (1993a). Asian affinities and continental radiation of the four founding Native American mtDNAs,Am. J. Hum. Genet. 53 563–590.

    Google Scholar 

  • Torroni, A., Sukernik, R. I., Schurr, T. G., Starikovskaya, Y. B., Cabell, M. F., Crawford, M. H., Comuzzie, A. G., and Wallace, D. C. (1993b). MtDNA variation of aboriginal Siberians reveals distinct genetic affinities with Native Americans,Am. J. Hum. Genet. 53 591–608.

    Google Scholar 

  • Torroni, A., Chen, Y., Semino, O., Santachiara-Beneceretti, A. S., Scott, C. R., Lott, M. T., Winter, M., and Wallace, D. C. (1994a). Mitochondrial DNA and Y-chromosome polymorphisms in four native American populations from southern Mexico,Am. J. Hum. Genet. 54 303–318.

    Google Scholar 

  • Torroni, A., Lott, M. R., Cabell, M. F., Chen. Y., Laverge, L., Wallace, D. C. (1994b). Mitochondrial DNA and the origin of Caucasians. Identification of ancient Caucasian-specific haplogroups, one of which is prone to a recurrent somatic duplication in the D-loop region,Am. J. Hum. Genet., in press.

  • Torroni, A., Miller, J. A., Moore, L. G., Zamudio, S., Zhuang, J., Droma, R., and Wallace, D. C. (1994c). Mitochondrial DNA analysis in Tibet. Implications for the origin of the Tibetan population and its adaptation to high altitude,Am. J. Phys. Anthropol.,93 189–199.

    Google Scholar 

  • Torroni, A., Neel, J. V., Barrantes, R., Schurr, T. G., and Wallace, D. C. (1994d). A mitochondrial DNA “clock” for the Amerinds and its implications for timing their entry into North America,Proc. Natl. Acad. Sci. USA,91 1158–1162.

    Google Scholar 

  • Trounce, I., Byrne, E., and Marzuki, S. (1989). Decline in skeletal muscle mitochondrial respiratory chain function: possible factor in ageing,Lancet 1 637–639.

    Google Scholar 

  • van den Ouweland, J. M., Lemkes, H. H. P., Ruitenbeek, W., Sandkjujl, L. A., deVijlder, M. F., Struyvenberg, P. A. A., van de Kamp, J. J. P., and Maassen, J. A. (1992). Mutation in mitochondrial tRNALeu(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness,Nature Genet. 1 368–371.

    Google Scholar 

  • Wallace, D. C. (1992a). Mitochondrial genetics: a paradigm for aging and degenerative diseases?Science 256 628–632.

    Google Scholar 

  • Wallace, D. C. (1992b). Diseases of the mitochondrial DNA,Annu. Rev. Biochem. 61 1175–1212.

    Google Scholar 

  • Wallace, D. C., Garrison, K., and Knowler, W. C. (1985). Dramatic founder effects in Amerindian mitochondrial DNAs,Am. J. Phys. Anthropol. 68 149–155.

    Google Scholar 

  • Wallace, D. C., Singh, G., Lott, M. T., Hodge, J. A., Schurr, T. G., Lezza, A. M., Elsas, L. J., and Nikoskelainen, E. K. (1988). Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy,Science 242 1427–1430.

    Google Scholar 

  • Wallace, D. C., Lott, M. R., Shoffner, J. M., and Ballinger, S. (1994a). Mitochondrial DNA mutations in epilepsy and neurological disease,Epilepsia 35(Suppl. 1), S43-S50.

    Google Scholar 

  • Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., and Shoffner, J. M. (1994b). Report of the committee on human mitochondrial DNA.Human Gene Mapping, 1993: A compendium. Baltimore: The Johns Hopkins University Press, (in press).

    Google Scholar 

  • Yen, T. C., Chen, Y. S., King, K. L., Yeh, S. H., and Wei, Y. H. (1989). Liver mitochondrial respiratory functions decline with age,Biochem. Biophys. Res. Commun. 165 944–1003.

    Google Scholar 

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

    Google Scholar 

  • Zeviani, M., Bresolin, N., Gellera, C., Bordoni, A., Pannacci, M., Amati, P., Moggio, M., Servidei, S., Scarlato, G., and DiDonato, S. (1990). Nucleus-driven multiple large-scale deletions of the human mitochondrial genome: a new autos-omal dominant disease,Am. J. Hum. Genet. 47 904–914.

    Google Scholar 

  • Zhang, C., Baumer, A., Maxwell, R. J., Linnane, A. W., and Nagley, P. (1992). Multiple mitochondrial DNA deletions in an elderly human individual,FEBS Lett. 297 4–8.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Genetics and Molecular Medicine, 1462 Clifton Road, Suite 446, Emory University School of Medicine, 30322, Atlanta, Georgia

    Douglas C. Wallace

Authors
  1. Douglas C. Wallace
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wallace, D.C. Mitochondrial DNA mutations in diseases of energy metabolism. J Bioenerg Biomembr 26, 241–250 (1994). https://doi.org/10.1007/BF00763096

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00763096

Key words

Search

Navigation