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PMID: 16285865 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine.

Annual review of genetics ·Vol. 39 ·2005-00-00 ·Pages 359-407

Wallace DC

Abstract

Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by-product, I hypothesize that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer. Because mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes essential genes for energy production, I propose that the delayed-onset and progressive course of the age-related diseases results from the accumulation of somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific manifestations of these diseases may result from the varying energetic roles and needs of the different tissues. The variation in the individual and regional predisposition to degenerative diseases and cancer may result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today.

MeSH Terms
Aging/metabolism Energy Metabolism Humans Longevity/genetics Metabolic Diseases/genetics,metabolism,pathology Mitochondria/genetics,metabolism,pathology Neoplasms/metabolism,pathology
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Wallace Douglas C
Center for Molecular and Mitochondrial Medicine and Genetics, Department of Ecology and Evolutionary Biology, University of California, Irvine, California 92697-3940, USA. dwallace@uci.edu
References (248)
248 references, click to expand
  1. Genetic pathways that regulate ageing in model organisms.
    Nature. 2000 Nov 9;408(6809):255-62 PMID: 11089983
  2. Functional analysis of lymphoblast and cybrid mitochondria containing the 3460, 11778, or 14484 Leber's hereditary optic neuropathy mitochondrial DNA mutation.
    J Biol Chem. 2000 Dec 22;275(51):39831-6 PMID: 10976107
  3. Extended life-span conferred by cotransporter gene mutations in Drosophila.
    Science. 2000 Dec 15;290(5499):2137-40 PMID: 11118146
  4. Amyloid-beta is an antioxidant for lipoproteins in cerebrospinal fluid and plasma.
    Free Radic Biol Med. 2001 Jan 1;30(1):119-28 PMID: 11134902
  5. Mitochondrial genome variation and the origin of modern humans.
    Nature. 2000 Dec 7;408(6813):708-13 PMID: 11130070
  6. Impact of apoE deficiency on oxidative insults and antioxidant levels in the brain.
    Brain Res Mol Brain Res. 2001 Jan 31;86(1-2):76-83 PMID: 11165374
  7. Increased mitochondrial oxidative stress in the Sod2 (+/-) mouse results in the age-related decline of mitochondrial function culminating in increased apoptosis.
    Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2278-83 PMID: 11226230
  8. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans.
    Nature. 2001 Mar 8;410(6825):227-30 PMID: 11242085
  9. A dietary source of coenzyme Q is essential for growth of long-lived Caenorhabditis elegans clk-1 mutants.
    Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):421-6 PMID: 11136229
  10. Muscle-specific mutations accumulate with aging in critical human mtDNA control sites for replication.
    Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4022-7 PMID: 11274426
  11. Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein.
    Science. 2001 Apr 6;292(5514):104-6 PMID: 11292874
  12. Elevated and altered expression of the multifunctional DNA base excision repair and redox enzyme Ape1/ref-1 in prostate cancer.
    Clin Cancer Res. 2001 Apr;7(4):824-30 PMID: 11309329
  13. Oxidative damage to mitochondrial DNA in spinal motoneurons of transgenic ALS mice.
    Brain Res Mol Brain Res. 2001 Apr 18;89(1-2):147-52 PMID: 11311985
  14. Altered quinone biosynthesis in the long-lived clk-1 mutants of Caenorhabditis elegans.
    J Biol Chem. 2001 Mar 16;276(11):7713-6 PMID: 11244089
  15. Mitochondrial DNA polymorphism: its role in longevity of the Irish population.
    Exp Gerontol. 2001 Jul;36(7):1161-78 PMID: 11404057
  16. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma.
    Am J Hum Genet. 2001 Jul;69(1):49-54 PMID: 11404820
  17. Energy hypometabolism in posterior cingulate cortex of Alzheimer's patients: superficial laminar cytochrome oxidase associated with disease duration.
    J Neurosci. 2001 Jul 1;21(13):4923-30 PMID: 11425920
  18. Genetics of Parkinsonism: a review.
    Ann Hum Genet. 2001 Mar;65(Pt 2):111-26 PMID: 11427172
  19. Novel mtDNA mutations and oxidative phosphorylation dysfunction in Russian LHON families.
    Hum Genet. 2001 Jul;109(1):33-9 PMID: 11479733
  20. Does oxidative damage to DNA increase with age?
    Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10469-74 PMID: 11517304
  21. Redox regulation of the DNA repair function of the human AP endonuclease Ape1/ref-1.
    Antioxid Redox Signal. 2001 Aug;3(4):671-83 PMID: 11554453
  22. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1.
    Nature. 2001 Sep 13;413(6852):131-8 PMID: 11557972
  23. Regulation of physiological rates in Caenorhabditis elegans by a tRNA-modifying enzyme in the mitochondria.
    Genetics. 2001 Sep;159(1):147-57 PMID: 11560893
  24. Paradoxes in longevity: sequence analysis of mtDNA haplogroup J in centenarians.
    Eur J Hum Genet. 2001 Sep;9(9):701-7 PMID: 11571560
  25. Mouse models for mitochondrial disease.
    Am J Med Genet. 2001 Spring;106(1):71-93 PMID: 11579427
  26. A fraction of yeast Cu,Zn-superoxide dismutase and its metallochaperone, CCS, localize to the intermembrane space of mitochondria. A physiological role for SOD1 in guarding against mitochondrial oxidative damage.
    J Biol Chem. 2001 Oct 12;276(41):38084-9 PMID: 11500508
  27. Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu,Zn-SOD in mitochondria.
    J Biol Chem. 2001 Oct 19;276(42):38388-93 PMID: 11507097
  28. Nonalcoholic fatty liver disease: relationship to insulin sensitivity and oxidative stress. Treatment approaches using vitamin E, magnesium, and betaine.
    Altern Med Rev. 2002 Aug;7(4):276-91 PMID: 12197781
  29. The coactivator PGC-1 is involved in the regulation of the liver carnitine palmitoyltransferase I gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB).
    J Biol Chem. 2002 Oct 11;277(41):37991-8000 PMID: 12107181
  30. The role of cytochrome c oxidase deficient hippocampal neurones in Alzheimer's disease.
    Neuropathol Appl Neurobiol. 2002 Oct;28(5):390-6 PMID: 12366820
  31. Transcriptional profile of aging in C. elegans.
    Curr Biol. 2002 Sep 17;12(18):1566-73 PMID: 12372248
  32. Role of mitochondrial dysfunction in Alzheimer's disease.
    J Neurosci Res. 2002 Nov 1;70(3):357-60 PMID: 12391597
  33. Amyloid-beta and tau serve antioxidant functions in the aging and Alzheimer brain.
    Free Radic Biol Med. 2002 Nov 1;33(9):1194-9 PMID: 12398927
  34. Accumulation of mitochondrial DNA mutations in ageing, cancer, and mitochondrial disease: is there a common mechanism?
    Lancet. 2002 Oct 26;360(9342):1323-5 PMID: 12414225
  35. Extensive somatic mitochondrial mutations in primary prostate cancer using laser capture microdissection.
    Cancer Res. 2002 Nov 15;62(22):6470-4 PMID: 12438238
  36. Mitochondrial DNA polymorphisms associated with longevity in a Finnish population.
    Hum Genet. 2003 Jan;112(1):29-33 PMID: 12483296
  37. A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity.
    Nat Genet. 2003 Jan;33(1):40-8 PMID: 12447374
  38. Natural selection shaped regional mtDNA variation in humans.
    Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):171-6 PMID: 12509511
  39. Extended longevity in mice lacking the insulin receptor in adipose tissue.
    Science. 2003 Jan 24;299(5606):572-4 PMID: 12543978
  40. Strikingly higher frequency in centenarians and twins of mtDNA mutation causing remodeling of replication origin in leukocytes.
    Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1116-21 PMID: 12538859
  41. Regulation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha ) and mitochondrial function by MEF2 and HDAC5.
    Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1711-6 PMID: 12578979
  42. Regulation of PGC-1 promoter activity by protein kinase B and the forkhead transcription factor FKHR.
    Diabetes. 2003 Mar;52(3):642-9 PMID: 12606503
  43. A Gly482Ser missense mutation in the peroxisome proliferator-activated receptor gamma coactivator-1 is associated with altered lipid oxidation and early insulin secretion in Pima Indians.
    Diabetes. 2003 Mar;52(3):895-8 PMID: 12606537
  44. Economic costs of diabetes in the US in 2002.
    Diabetes Care. 2003 Mar;26(3):917-32 PMID: 12610059
  45. Control region mtDNA variants: longevity, climatic adaptation, and a forensic conundrum.
    Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2174-6 PMID: 12606714
  46. Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease.
    Am J Hum Genet. 2003 Apr;72(4):804-11 PMID: 12618962
  47. Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease.
    Curr Opin Cell Biol. 2003 Apr;15(2):241-6 PMID: 12648681
  48. Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells.
    J Cell Biol. 2003 Apr 14;161(1):41-54 PMID: 12695498
  49. DAF-16 target genes that control C. elegans life-span and metabolism.
    Science. 2003 Apr 25;300(5619):644-7 PMID: 12690206
  50. Minireview: lipid metabolism, metabolic diseases, and peroxisome proliferator-activated receptors.
    Endocrinology. 2003 Jun;144(6):2201-7 PMID: 12746275
  51. Mitochondrial respiratory-chain diseases.
    N Engl J Med. 2003 Jun 26;348(26):2656-68 PMID: 12826641
  52. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes.
    Nat Genet. 2003 Jul;34(3):267-73 PMID: 12808457
  53. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1.
    Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8466-71 PMID: 12832613
  54. Suppression of beta cell energy metabolism and insulin release by PGC-1alpha.
    Dev Cell. 2003 Jul;5(1):73-83 PMID: 12852853
  55. Alzheimer disease in the US population: prevalence estimates using the 2000 census.
    Arch Neurol. 2003 Aug;60(8):1119-22 PMID: 12925369
  56. Autophagy genes are essential for dauer development and life-span extension in C. elegans.
    Science. 2003 Sep 5;301(5638):1387-91 PMID: 12958363
  57. Mitochondrial proteome: altered cytochrome c oxidase subunit levels in prostate cancer.
    Proteomics. 2003 Sep;3(9):1801-10 PMID: 12973739
  58. Bilateral striatal necrosis associated with a novel mutation in the mitochondrial ND6 gene.
    Ann Neurol. 2003 Oct;54(4):527-30 PMID: 14520668
  59. Forkhead transcription factor FOXO1 (FKHR)-dependent induction of PDK4 gene expression in skeletal muscle during energy deprivation.
    Biochem J. 2003 Oct 15;375(Pt 2):365-71 PMID: 12820900
  60. Alpha-synuclein expression in HEK293 cells enhances the mitochondrial sensitivity to rotenone.
    Neurosci Lett. 2003 Nov 6;351(1):29-32 PMID: 14550906
  61. PPARgamma coactivator 1beta/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity.
    Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12378-83 PMID: 14530391
  62. Aging-dependent large accumulation of point mutations in the human mtDNA control region for replication.
    Science. 1999 Oct 22;286(5440):774-9 PMID: 10531063
  63. Familial multisystem degeneration with parkinsonism associated with the 11778 mitochondrial DNA mutation.
    Neurology. 1999 Nov 10;53(8):1787-93 PMID: 10563629
  64. Mitochondrial DNA variation in human evolution and disease.
    Gene. 1999 Sep 30;238(1):211-30 PMID: 10570998
  65. The p66shc adaptor protein controls oxidative stress response and life span in mammals.
    Nature. 1999 Nov 18;402(6759):309-13 PMID: 10580504
  66. Induction of autophagy and inhibition of tumorigenesis by beclin 1.
    Nature. 1999 Dec 9;402(6762):672-6 PMID: 10604474
  67. Mitochondrial DNA rearrangements in aging human brain and in situ PCR of mtDNA.
    Neurobiol Aging. 1999 Sep-Oct;20(5):565-71 PMID: 10638530
  68. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.
    Science. 2000 Feb 4;287(5454):848-51 PMID: 10657297
  69. The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes.
    Mol Cell Biol. 2000 Mar;20(5):1868-76 PMID: 10669761
  70. Oxidative insults are associated with apolipoprotein E genotype in Alzheimer's disease brain.
    Neurobiol Dis. 2000 Feb;7(1):23-37 PMID: 10671320
  71. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase.
    Nature. 2000 Feb 17;403(6771):795-800 PMID: 10693811
  72. Facile detection of mitochondrial DNA mutations in tumors and bodily fluids.
    Science. 2000 Mar 17;287(5460):2017-9 PMID: 10720328
  73. Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes.
    Cell. 2000 Mar 17;100(6):645-54 PMID: 10761930
  74. Beta-cell mitochondria in the regulation of insulin secretion: a new culprit in type II diabetes.
    Diabetologia. 2000 Mar;43(3):265-77 PMID: 10768087
  75. Somatic mitochondrial DNA (mtDNA) mutations in papillary thyroid carcinomas and differential mtDNA sequence variants in cases with thyroid tumours.
    Oncogene. 2000 Apr 13;19(16):2060-6 PMID: 10803467
  76. Decreased hippocampal metabolic activity in Alzheimer patients is not reflected in the immunoreactivity of cytochrome oxidase subunits.
    Exp Neurol. 2000 Jun;163(2):440-51 PMID: 10833319
  77. The evolution of free radicals and oxidative stress.
    Am J Med. 2000 Jun 1;108(8):652-9 PMID: 10856414
  78. Mitochondrial DNA sequence diversity in bipolar affective disorder.
    Am J Psychiatry. 2000 Jul;157(7):1058-64 PMID: 10873911
  79. Gene-expression profile of the ageing brain in mice.
    Nat Genet. 2000 Jul;25(3):294-7 PMID: 10888876
  80. Antioxidant enzyme expression and reactive oxygen species damage in prostatic intraepithelial neoplasia and cancer.
    Cancer. 2000 Jul 1;89(1):123-34 PMID: 10897009
  81. alpha-synuclein promotes mitochondrial deficit and oxidative stress.
    Am J Pathol. 2000 Aug;157(2):401-10 PMID: 10934145
  82. Molecular genetics of Alzheimer's disease: the role of beta-amyloid and the presenilins.
    Curr Opin Neurol. 2000 Aug;13(4):377-84 PMID: 10970053
  83. Extension of life-span with superoxide dismutase/catalase mimetics.
    Science. 2000 Sep 1;289(5484):1567-9 PMID: 10968795
  84. The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes.
    Nat Genet. 2000 Sep;26(1):76-80 PMID: 10973253
  85. Mitochondrial genotype associated with longevity and its inhibitory effect on mutagenesis.
    Mech Ageing Dev. 2000 Jul 31;116(2-3):65-76 PMID: 10996007
  86. Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis.
    J Clin Invest. 2000 Oct;106(7):847-56 PMID: 11018072
  87. Going APE over ref-1.
    Mutat Res. 2000 Oct 16;461(2):83-108 PMID: 11018583
  88. Levodopa motor complications in Parkinson's disease.
    Trends Neurosci. 2000 Oct;23(10 Suppl):S2-7 PMID: 11052214
  89. The age-related accumulation of a mitochondrial DNA control region mutation in muscle, but not brain, detected by a sensitive PNA-directed PCR clamping based method.
    Nucleic Acids Res. 2000 Nov 1;28(21):4350-5 PMID: 11058135
  90. Mutations in SDHC cause autosomal dominant paraganglioma, type 3.
    Nat Genet. 2000 Nov;26(3):268-70 PMID: 11062460
  91. Impaired insulin secretion and beta-cell loss in tissue-specific knockout mice with mitochondrial diabetes.
    Nat Genet. 2000 Nov;26(3):336-40 PMID: 11062475
  92. Cytoplasmic inheritance of chloramphenicol resistance in mouse tissue culture cells.
    Proc Natl Acad Sci U S A. 1974 May;71(5):1681-5 PMID: 4525288
  93. Cytoplasmic transfer of chloramphenicol resistance in human tissue culture cells.
    J Cell Biol. 1975 Oct;67(1):174-88 PMID: 1176530
  94. Maternal inheritance of human mitochondrial DNA.
    Proc Natl Acad Sci U S A. 1980 Nov;77(11):6715-9 PMID: 6256757
  95. Association of mitochondrial DNA damage with aging and coronary atherosclerotic heart disease.
    Mutat Res. 1992 Sep;275(3-6):169-80 PMID: 1383759
  96. Energy metabolism and aging: a lifelong study of Fischer 344 rats.
    Am J Physiol. 1992 Sep;263(3 Pt 1):E448-52 PMID: 1415524
  97. Dietary restriction alters characteristics of glucose fuel use.
    J Gerontol. 1992 Nov;47(6):B202-8 PMID: 1430849
  98. Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion.
    Nat Genet. 1992 Apr;1(1):11-5 PMID: 1301992
  99. Mosaicism for a specific somatic mitochondrial DNA mutation in adult human brain.
    Nat Genet. 1992 Dec;2(4):318-23 PMID: 1303287
  100. Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age.
    Nat Genet. 1992 Dec;2(4):324-9 PMID: 1303288
  101. Mitochondrial DNA variants observed in Alzheimer disease and Parkinson disease patients.
    Genomics. 1993 Jul;17(1):171-84 PMID: 8104867
  102. Dietary restriction and aging.
    J Am Geriatr Soc. 1993 Sep;41(9):994-9 PMID: 8409187
  103. Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain.
    Ann Neurol. 1993 Oct;34(4):609-16 PMID: 8215249
  104. Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster.
    Science. 1994 Feb 25;263(5150):1128-30 PMID: 8108730
  105. Maternally inherited diabetes and deafness is a distinct subtype of diabetes and associates with a single point mutation in the mitochondrial tRNA(Leu(UUR)) gene.
    Diabetes. 1994 Jun;43(6):746-51 PMID: 7910800
  106. A mitochondrial DNA mutation at nucleotide pair 14459 of the NADH dehydrogenase subunit 6 gene associated with maternally inherited Leber hereditary optic neuropathy and dystonia.
    Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6206-10 PMID: 8016139
  107. Cytoplasmic transfer of the mtDNA nt 8993 T-->G (ATP6) point mutation associated with Leigh syndrome into mtDNA-less cells demonstrates cosegregation with a decrease in state III respiration and ADP/O ratio.
    Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8334-8 PMID: 8078883
  108. Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse.
    Mech Ageing Dev. 1994 May;74(1-2):121-33 PMID: 7934203
  109. Mitochondrial diabetes revisited.
    Nat Genet. 1994 Aug;7(4):458-9 PMID: 7951312
  110. Cortical cytochrome oxidase activity is reduced in Alzheimer's disease.
    J Neurochem. 1994 Dec;63(6):2179-84 PMID: 7964738
  111. Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease.
    Ann Neurol. 1994 Nov;36(5):747-51 PMID: 7979220
  112. Marked changes in mitochondrial DNA deletion levels in Alzheimer brains.
    Genomics. 1994 Sep 15;23(2):471-6 PMID: 7835898
  113. A mitochondrial DNA clone is associated with increased risk for Alzheimer disease.
    Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6892-5 PMID: 7624338
  114. Marked increase in mitochondrial DNA deletion levels in the cerebral cortex of Huntington's disease patients.
    Neurology. 1995 Oct;45(10):1879-83 PMID: 7477986
  115. Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency.
    Nat Genet. 1995 Oct;11(2):144-9 PMID: 7550341
  116. Marked increase in the number and variety of mitochondrial DNA rearrangements in aging human skeletal muscle.
    Nucleic Acids Res. 1995 Oct 25;23(20):4122-6 PMID: 7479075
  117. Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase.
    Nat Genet. 1995 Dec;11(4):376-81 PMID: 7493016
  118. Morphological, biochemical, and genetic support for an apolipoprotein E effect on microtubular metabolism.
    Ann N Y Acad Sci. 1996 Jan 17;777:146-57 PMID: 8624078
  119. Assessment of mitochondrial oxidative phosphorylation in patient muscle biopsies, lymphoblasts, and transmitochondrial cell lines.
    Methods Enzymol. 1996;264:484-509 PMID: 8965721
  120. Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides.
    Nat Genet. 1996 Sep;14(1):55-61 PMID: 8782820
  121. Novel mitochondrial DNA deletion found in a renal cell carcinoma.
    Genes Chromosomes Cancer. 1996 Feb;15(2):95-101 PMID: 8834172
  122. A novel gly290asp mitochondrial cytochrome b mutation linked to a complex III deficiency in progressive exercise intolerance.
    Mol Cell Probes. 1996 Oct;10(5):389-91 PMID: 8910895
  123. Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage.
    Am J Hum Genet. 1997 Feb;60(2):381-7 PMID: 9012411
  124. Multi-organ characterization of mitochondrial genomic rearrangements in ad libitum and caloric restricted mice show striking somatic mitochondrial DNA rearrangements with age.
    Nucleic Acids Res. 1997 Mar 1;25(5):974-82 PMID: 9023106
  125. Detection of somatic mutations in the mitochondrial DNA control region of colorectal and gastric tumors by heteroduplex and single-strand conformation analysis.
    Electrophoresis. 1997 May;18(5):682-5 PMID: 9194590
  126. CuZn superoxide dismutase (SOD1) accumulates in vacuolated mitochondria in transgenic mice expressing amyotrophic lateral sclerosis-linked SOD1 mutations.
    Acta Neuropathol. 2001 Oct;102(4):293-305 PMID: 11603803
  127. Lifespan extension and rescue of spongiform encephalopathy in superoxide dismutase 2 nullizygous mice treated with superoxide dismutase-catalase mimetics.
    J Neurosci. 2001 Nov 1;21(21):8348-53 PMID: 11606622
  128. Negative control of p53 by Sir2alpha promotes cell survival under stress.
    Cell. 2001 Oct 19;107(2):137-48 PMID: 11672522
  129. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase.
    Cell. 2001 Oct 19;107(2):149-59 PMID: 11672523
  130. Amyloid-beta: an antioxidant that becomes a pro-oxidant and critically contributes to Alzheimer's disease.
    Free Radic Biol Med. 2001 Nov 1;31(9):1120-31 PMID: 11677045
  131. A defect in the cytochrome b large subunit in complex II causes both superoxide anion overproduction and abnormal energy metabolism in Caenorhabditis elegans.
    J Biol Chem. 2001 Nov 9;276(45):41553-8 PMID: 11527963
  132. Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans.
    Dev Cell. 2001 Nov;1(5):633-44 PMID: 11709184
  133. Genetics of lifespan in C. elegans: molecular diversity, physiological complexity, mechanistic simplicity.
    Trends Genet. 2001 Dec;17(12):712-8 PMID: 11718925
  134. Global and societal implications of the diabetes epidemic.
    Nature. 2001 Dec 13;414(6865):782-7 PMID: 11742409
  135. Model organisms as a guide to mammalian aging.
    Dev Cell. 2002 Jan;2(1):9-19 PMID: 11782310
  136. Mutation analysis of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) and relationships of identified amino acid polymorphisms to Type II diabetes mellitus.
    Diabetologia. 2001 Dec;44(12):2220-6 PMID: 11793024
  137. Formation and removal of alpha-synuclein aggregates in cells exposed to mitochondrial inhibitors.
    J Biol Chem. 2002 Feb 15;277(7):5411-7 PMID: 11724769
  138. Comprehensive scanning of somatic mitochondrial DNA mutations in breast cancer.
    Cancer Res. 2002 Feb 15;62(4):972-6 PMID: 11861366
  139. Oxidative processes in the brain and non-neuronal tissues as biomarkers of Alzheimer's disease.
    Front Biosci. 2002 Apr 1;7:d1007-15 PMID: 11897553
  140. The role of mtDNA background in disease expression: a new primary LHON mutation associated with Western Eurasian haplogroup J.
    Hum Genet. 2002 Feb;110(2):130-8 PMID: 11935318
  141. Dietary restriction in long-lived dwarf flies.
    Science. 2002 Apr 12;296(5566):319 PMID: 11951037
  142. Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer's disease.
    Neurobiol Aging. 2002 May-Jun;23(3):371-6 PMID: 11959398
  143. Alzheimer's disease and oxygen radicals: new insights.
    Biochem Pharmacol. 2002 Feb 15;63(4):563-7 PMID: 11992623
  144. Mitochondrial DNA somatic mutations (point mutations and large deletions) and mitochondrial DNA variants in human thyroid pathology: a study with emphasis on Hürthle cell tumors.
    Am J Pathol. 2002 May;160(5):1857-65 PMID: 12000737
  145. Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence.
    EMBO J. 2002 May 15;21(10):2383-96 PMID: 12006491
  146. Genome-wide transcript profiles in aging and calorically restricted Drosophila melanogaster.
    Curr Biol. 2002 Apr 30;12(9):712-23 PMID: 12007414
  147. Nuclear activators and coactivators in mammalian mitochondrial biogenesis.
    Biochim Biophys Acta. 2002 Jun 7;1576(1-2):1-14 PMID: 12031478
  148. A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis.
    Oncogene. 2002 May 30;21(24):3872-8 PMID: 12032825
  149. Overexpression of manganese superoxide dismutase attenuates neuronal death in human cells expressing mutant (G37R) Cu/Zn-superoxide dismutase.
    J Neurochem. 2002 Apr;81(1):170-7 PMID: 12067230
  150. Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster.
    Genetics. 2002 Jun;161(2):661-72 PMID: 12072463
  151. Amyotrophic lateral sclerosis: a proposed mechanism.
    Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):9010-4 PMID: 12060716
  152. Mitochondrial DNA alterations in cancer.
    Cancer Invest. 2002;20(4):557-69 PMID: 12094550
  153. Presenilin-1 is located in rat mitochondria.
    Biochem Biophys Res Commun. 2002 Jul 19;295(3):766-70 PMID: 12099705
  154. Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines.
    Nat Neurosci. 2002 Aug;5(8):731-6 PMID: 12089530
  155. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres.
    Nature. 2002 Aug 15;418(6899):797-801 PMID: 12181572
  156. Hypoxemia is associated with mitochondrial DNA damage and gene induction. Implications for cardiac disease.
    JAMA. 1991 Oct 2;266(13):1812-6 PMID: 1890710
  157. Targeting of hexokinase 1 to liver and hepatoma mitochondria.
    Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):202-6 PMID: 1309605
  158. The structure of human mitochondrial DNA variation.
    J Mol Evol. 1991 Dec;33(6):543-55 PMID: 1685753
  159. Heteroplasmic mtDNA mutation (T----G) at 8993 can cause Leigh disease when the percentage of abnormal mtDNA is high.
    Am J Hum Genet. 1992 Apr;50(4):852-8 PMID: 1550128
  160. Mitochondrial genetics: a paradigm for aging and degenerative diseases?
    Science. 1992 May 1;256(5057):628-32 PMID: 1533953
  161. Diseases of the mitochondrial DNA.
    Annu Rev Biochem. 1992;61:1175-212 PMID: 1497308
  162. Correlation of sperm motility with mitochondrial enzymatic activities.
    Clin Chem. 1998 Aug;44(8 Pt 1):1616-20 PMID: 9702947
  163. A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes.
    Nature. 1998 Aug 13;394(6694):694-7 PMID: 9716135
  164. Somatic mutations of the mitochondrial genome in human colorectal tumours.
    Nat Genet. 1998 Nov;20(3):291-3 PMID: 9806551
  165. A nonsense mutation (G15059A) in the cytochrome b gene in a patient with exercise intolerance and myoglobinuria.
    Ann Neurol. 1999 Jan;45(1):127-30 PMID: 9894887
  166. Mutations in the promoter reveal a cause for the reduced expression of the human manganese superoxide dismutase gene in cancer cells.
    Oncogene. 1999 Jan 7;18(1):93-102 PMID: 9926924
  167. Decreased brain protein levels of cytochrome oxidase subunits in Alzheimer's disease and in hereditary spinocerebellar ataxia disorders: a nonspecific change?
    J Neurochem. 1999 Feb;72(2):700-7 PMID: 9930743
  168. Mitochondrial disease in superoxide dismutase 2 mutant mice.
    Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):846-51 PMID: 9927656
  169. Mitochondrial diseases in man and mouse.
    Science. 1999 Mar 5;283(5407):1482-8 PMID: 10066162
  170. Mitochondrial enzyme expression in the hippocampus in relation to Alzheimer-type pathology.
    Acta Neuropathol. 1999 Apr;97(4):346-54 PMID: 10208273
  171. Mitochondrial disease in mouse results in increased oxidative stress.
    Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):4820-5 PMID: 10220377
  172. Phylogenetic analysis of the mitochondrial genome indicates significant differences between patients with Alzheimer disease and controls in a French-Canadian founder population.
    Am J Med Genet. 1999 Jul 2;85(1):20-30 PMID: 10377009
  173. The A beta peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction.
    Biochemistry. 1999 Jun 15;38(24):7609-16 PMID: 10386999
  174. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1.
    Cell. 1999 Jul 9;98(1):115-24 PMID: 10412986
  175. Loss of heteroplasmy in the displacement loop of brain mitochondrial DNA in astrocytic tumors.
    Genes Chromosomes Cancer. 1999 Sep;26(1):80-3 PMID: 10441009
  176. A stop-codon mutation in the human mtDNA cytochrome c oxidase I gene disrupts the functional structure of complex IV.
    Am J Hum Genet. 1999 Sep;65(3):611-20 PMID: 10441567
  177. Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans.
    FASEB J. 1999 Sep;13(12):1532-6 PMID: 10463944
  178. Gene expression profile of aging and its retardation by caloric restriction.
    Science. 1999 Aug 27;285(5432):1390-3 PMID: 10464095
  179. beta-Amyloid fragment 25-35 selectively decreases complex IV activity in isolated mitochondria.
    FEBS Lett. 1999 Aug 20;457(1):131-4 PMID: 10486579
  180. Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization.
    Nat Med. 1999 Oct;5(10):1194-8 PMID: 10502825
  181. Mitochondrial gene mutation, but not large-scale deletion, is a feature of colorectal carcinomas with mitochondrial microsatellite instability.
    Int J Cancer. 1999 Nov 26;83(5):625-9 PMID: 10521798
  182. A cluster of metabolic defects caused by mutation in a mitochondrial tRNA.
    Science. 2004 Nov 12;306(5699):1190-4 PMID: 15498972
  183. Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria.
    J Biol Chem. 2004 Dec 3;279(49):51654-60 PMID: 15456764
  184. mtDNA mutations increase tumorigenicity in prostate cancer.
    Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):719-24 PMID: 15647368
  185. Copper-dependent inhibition of human cytochrome c oxidase by a dimeric conformer of amyloid-beta1-42.
    J Neurosci. 2005 Jan 19;25(3):672-9 PMID: 15659604
  186. Molecular links between aging and adipose tissue.
    Int J Obes (Lond). 2005 Mar;29 Suppl 1:S36-9 PMID: 15711582
  187. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1.
    Nature. 2005 Mar 3;434(7029):113-8 PMID: 15744310
  188. SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha}.
    J Biol Chem. 2005 Apr 22;280(16):16456-60 PMID: 15716268
  189. Extension of murine life span by overexpression of catalase targeted to mitochondria.
    Science. 2005 Jun 24;308(5730):1909-11 PMID: 15879174
  190. Cytochrome c oxidase is decreased in Alzheimer's disease platelets.
    Neurobiol Aging. 2004 Jan;25(1):105-10 PMID: 14675736
  191. Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging.
    Physiol Genomics. 2003 Dec 16;16(1):29-37 PMID: 14679299
  192. Early-onset renal cell carcinoma as a novel extraparaganglial component of SDHB-associated heritable paraganglioma.
    Am J Hum Genet. 2004 Jan;74(1):153-9 PMID: 14685938
  193. Biallelic inactivation of fumarate hydratase (FH) occurs in nonsyndromic uterine leiomyomas but is rare in other tumors.
    Am J Pathol. 2004 Jan;164(1):17-22 PMID: 14695314
  194. Effects of purifying and adaptive selection on regional variation in human mtDNA.
    Science. 2004 Jan 9;303(5655):223-6 PMID: 14716012
  195. Mitochondrial DNA-like sequences in the nucleus (NUMTs): insights into our African origins and the mechanism of foreign DNA integration.
    Hum Mutat. 2004 Feb;23(2):125-33 PMID: 14722916
  196. Calorie restriction extends yeast life span by lowering the level of NADH.
    Genes Dev. 2004 Jan 1;18(1):12-6 PMID: 14724176
  197. The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore.
    Nature. 2004 Jan 29;427(6973):461-5 PMID: 14749836
  198. Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer's disease worsen with passage in culture.
    Neurobiol Dis. 2004 Feb;15(1):29-39 PMID: 14751768
  199. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes.
    N Engl J Med. 2004 Feb 12;350(7):664-71 PMID: 14960743
  200. Mammalian SIRT1 represses forkhead transcription factors.
    Cell. 2004 Feb 20;116(4):551-63 PMID: 14980222
  201. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function.
    Genes Dev. 2004 Feb 15;18(4):357-68 PMID: 15004004
  202. Molecular regulation of angiogenesis and tumorigenesis by signal transduction pathways: evidence of predictable and reproducible patterns of synergy in diverse neoplasms.
    Semin Cancer Biol. 2004 Apr;14(2):81-91 PMID: 15018892
  203. The mtDNA T8993G (NARP) mutation results in an impairment of oxidative phosphorylation that can be improved by antioxidants.
    Hum Mol Genet. 2004 Apr 15;13(8):869-79 PMID: 14998933
  204. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase.
    Science. 2004 Mar 26;303(5666):2011-5 PMID: 14976264
  205. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease.
    Science. 2004 Apr 16;304(5669):448-52 PMID: 15087549
  206. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice.
    J Biol Chem. 2004 Apr 30;279(18):18614-22 PMID: 14985362
  207. Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle.
    Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6570-5 PMID: 15100410
  208. FoxOs at the crossroads of cellular metabolism, differentiation, and transformation.
    Cell. 2004 May 14;117(4):421-6 PMID: 15137936
  209. Hereditary early-onset Parkinson's disease caused by mutations in PINK1.
    Science. 2004 May 21;304(5674):1158-60 PMID: 15087508
  210. Premature ageing in mice expressing defective mitochondrial DNA polymerase.
    Nature. 2004 May 27;429(6990):417-23 PMID: 15164064
  211. The life span determinant p66Shc localizes to mitochondria where it associates with mitochondrial heat shock protein 70 and regulates trans-membrane potential.
    J Biol Chem. 2004 Jun 11;279(24):25689-95 PMID: 15078873
  212. Prostate cancer incidence and mortality rates and trends in the United States and Canada.
    Public Health Rep. 2004 Mar-Apr;119(2):174-86 PMID: 15192905
  213. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma.
    Nature. 2004 Jun 17;429(6993):771-6 PMID: 15175761
  214. Analysis of European mitochondrial haplogroups with Alzheimer disease risk.
    Neurosci Lett. 2004 Jul 15;365(1):28-32 PMID: 15234467
  215. Amyloid-beta: phylogenesis of a chameleon.
    Brain Res Brain Res Rev. 2004 Aug;46(1):118-20 PMID: 15297156
  216. The interaction between FOXO and SIRT1: tipping the balance towards survival.
    Trends Cell Biol. 2004 Aug;14(8):408-12 PMID: 15308206
  217. PGC-1alpha: turbocharging mitochondria.
    Cell. 2004 Oct 1;119(1):5-7 PMID: 15454076
  218. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice.
    Cell. 2004 Oct 1;119(1):121-35 PMID: 15454086
  219. Alternative translation initiation generates a novel isoform of insulin-degrading enzyme targeted to mitochondria.
    Biochem J. 2004 Nov 1;383(Pt. 3):439-46 PMID: 15285718
  220. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease.
    Science. 1997 Jun 27;276(5321):2045-7 PMID: 9197268
  221. Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin.
    Nat Genet. 1997 Aug;16(4):345-51 PMID: 9241270
  222. Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the frataxin homologue.
    Nat Genet. 1997 Aug;16(4):352-7 PMID: 9241271
  223. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans.
    Science. 1997 Aug 15;277(5328):942-6 PMID: 9252323
  224. Expression of antioxidant enzymes in human prostatic adenocarcinoma.
    Prostate. 1997 Sep 1;32(4):229-33 PMID: 9288180
  225. Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia.
    Nat Genet. 1997 Oct;17(2):215-7 PMID: 9326946
  226. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans.
    Nature. 1997 Oct 30;389(6654):994-9 PMID: 9353126
  227. Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease.
    Ann Neurol. 1998 Jan;43(1):110-6 PMID: 9450776
  228. Mitochondrial genotype associated with longevity.
    Lancet. 1998 Jan 17;351(9097):185-6 PMID: 9449878
  229. A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase.
    Nat Genet. 1998 Feb;18(2):159-63 PMID: 9462746
  230. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis.
    Cell. 1998 Mar 20;92(6):829-39 PMID: 9529258
  231. Genetic, metabolic and clinical characteristics of maturity onset diabetes of the young.
    Eur J Endocrinol. 1998 Mar;138(3):233-9 PMID: 9539292
  232. Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons.
    Nat Genet. 1998 Jun;19(2):171-4 PMID: 9620775
  233. Structure and evolution of organelle genomes.
    Microbiol Rev. 1982 Jun;46(2):208-40 PMID: 6750346
  234. Radiation of human mitochondria DNA types analyzed by restriction endonuclease cleavage patterns.
    J Mol Evol. 1983;19(3-4):255-71 PMID: 6310133
  235. Mitochondrial DNA and human evolution.
    Nature. 1987 Jan 1-7;325(6099):31-6 PMID: 3025745
  236. Genetic differences in effects of food restriction on aging in mice.
    J Nutr. 1987 Feb;117(2):376-82 PMID: 3559752
  237. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies.
    Nature. 1988 Feb 25;331(6158):717-9 PMID: 2830540
  238. Hexose metabolism in pancreatic islets: regulation of mitochondrial hexokinase binding.
    Biochem Med Metab Biol. 1988 Feb;39(1):80-9 PMID: 3281698
  239. Familial mitochondrial encephalomyopathy (MERRF): genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease.
    Cell. 1988 Nov 18;55(4):601-10 PMID: 3180221
  240. Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy.
    Science. 1988 Dec 9;242(4884):1427-30 PMID: 3201231
  241. Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome.
    N Engl J Med. 1989 May 18;320(20):1293-9 PMID: 2541333
  242. Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation.
    Science. 1989 Oct 27;246(4929):500-3 PMID: 2814477
  243. Detection of hydroxyl radical in the mitochondria of ischemic-reperfused myocardium by trapping with salicylate.
    Biochem Biophys Res Commun. 1989 Dec 29;165(3):1004-9 PMID: 2558644
  244. A new mitochondrial disease associated with mitochondrial DNA heteroplasmy.
    Am J Hum Genet. 1990 Mar;46(3):428-33 PMID: 2137962
  245. Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation.
    Cell. 1990 Jun 15;61(6):931-7 PMID: 2112427
  246. A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies.
    Nature. 1990 Dec 13;348(6302):651-3 PMID: 2102678
  247. Detection of a specific mitochondrial DNA deletion in tissues of older humans.
    Nucleic Acids Res. 1990 Dec 11;18(23):6927-33 PMID: 2263455
  248. Porin interaction with hexokinase and glycerol kinase: metabolic microcompartmentation at the outer mitochondrial membrane.
    Biochem Med Metab Biol. 1991 Jun;45(3):271-91 PMID: 1710914
Article Info
Journal
Annual review of genetics
Abbr.
Annu Rev Genet
ISSN
0066-4197
DOI
10.1146/annurev.genet.39.110304.095751
Email
dwallace@uci.edu
Published
2005-00-00
Pages
359-407
Language
English
Region
United States
NLM ID
0117605
PMCID
PMC2821041
Subset
IM
Grants
NINDS NIH HHS · NS21328 · United States
NINDS NIH HHS · R01 NS041850 · United States
NIA NIH HHS · R01 AG024373-02 · United States
FIC NIH HHS · TW01366 · United States
NINDS NIH HHS · NS41650 · United States
NIA NIH HHS · R01 AG013154-11 · United States
FIC NIH HHS · R03 TW001366-04 · United States
NIA NIH HHS · R01 AG024373-01 · United States
FIC NIH HHS · R03 TW001366 · United States
NINDS NIH HHS · R01 NS041850-06 · United States
NIA NIH HHS · AG24373 · United States
NHLBI NIH HHS · HL64017 · United States
NIA NIH HHS · R01 AG024373 · United States
NINDS NIH HHS · R01 NS021328-21 · United States
NINDS NIH HHS · R01 NS021328 · United States
NIA NIH HHS · R01 AG013154 · United States
NIA NIH HHS · AG13154 · United States
External Links
PubMed source DOI: 10.1146/annurev.genet.39.110304.095751 PMC Full Text View journal details
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