Human mitochondrial DNA: Roles of inherited and somatic mutations

Nature Reviews Genetics

Volumn 13, Issue 12, 2012, Pages 878-890

  Schon, Eric A ^a   Dimauro, Salvatore ^a   Hirano, Michio ^a  

^a Department of Medicine   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME C OXIDASE; FUMARATE HYDRATASE; HYPOXIA INDUCIBLE FACTOR 1; MITOCHONDRIAL DNA; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); RIBOSOME RNA; RNA 16S; SUCCINATE DEHYDROGENASE; TRANSFER RNA; UBIQUINOL CYTOCHROME C REDUCTASE; VOLTAGE DEPENDENT ANION CHANNEL 1;

AGING; CELL DEATH; CHROMOSOMAL INSTABILITY; GENE MUTATION; GENE PRODUCT; GENETIC SUSCEPTIBILITY; HUMAN; KEARNS SAYRE SYNDROME; LEBER HEREDITARY OPTIC NEUROPATHY; MELAS SYNDROME; MEMBRANE POTENTIAL; MERRF SYNDROME; NARP SYNDROME; NERVE DEGENERATION; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; SOMATIC MUTATION;

AGING; DNA, MITOCHONDRIAL; ELECTRON TRANSPORT; GENOME, MITOCHONDRIAL; GERM-LINE MUTATION; HEREDODEGENERATIVE DISORDERS, NERVOUS SYSTEM; HUMANS; MITOCHONDRIAL DISEASES; MODELS, BIOLOGICAL; MODELS, GENETIC; MUTATION; NEOPLASMS; OXIDATIVE PHOSPHORYLATION;

EID: 84869397441     PISSN: 14710056     EISSN: 14710064     Source Type: Journal    
DOI: 10.1038/nrg3275     Document Type: Review

References (149)

1. Sagan, L. On the origin of mitosing cells. J. Theor. Biol. 14, 255-274 (1967).
2. Garcia-Rodriguez, L. J. Appendix 1. Basic properties of mitochondria. Methods Cell Biol. 80, 809-812 (2007).
3. Calvo, S. E. et al. Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing. Sci. Transl. Med. 4, 118ra10 (2012).
4. Schaefer, A. M. et al. Prevalence of mitochondrial DNA disease in adults. Ann. Neurol. 63, 35-39 (2008). (Pubitemid 351240549)
5. Greaves, L. C., Reeve, A. K., Taylor, R. W. & Turnbull, D. M. Mitochondrial DNA and disease. J. Pathol. 226, 274-286 (2012).
6. Koopman, W. J., Willems, P. H. & Smeitink, J. A. Monogenic mitochondrial disorders. N. Engl. J. Med. 366, 1132-1141 (2012).
7. Ylikallio, E. & Suomalainen, A. Mechanisms of mitochondrial diseases. Ann. Med. 44, 41-59 (2012).
8. Anderson, S. et al. Sequence and organization of the human mitochondrial genome. Nature 290, 457-465 (1981). (Pubitemid 11159074)
9. DiMauro, S. & Schon, E. A. Mitochondrial respiratory-chain diseases. N. Engl. J. Med. 348, 2656-2668 (2003). (Pubitemid 36741594)
10. Sacconi, S. et al. A functionally dominant mitochondrial DNA mutation. Hum. Mol. Genet. 17, 1814-1820 (2008). (Pubitemid 351791508)
11. Yoneda, M., Miyatake, T. & Attardi, G. Heteroplasmic mitochondrial tRNALys mutation and its complementation in MERRF patient-derived mitochondrial transformants. Muscle Nerve 3, S95-S101 (1995).
12. Sciacco, M., Bonilla, E., Schon, E. A., DiMauro, S. & Moraes, C. T. Distribution of wild-type and common deletion forms of mtDNA in normal and respiration-deficient muscle fibers from patients with mitochondrial myopathy. Hum. Mol. Genet. 3, 13-19 (1994). (Pubitemid 24038136)
13. Santorelli, F. M., Shanske, S., Macaya, A., DeVivo, D. C. & DiMauro, S. The mutation at nt 8993 of mitochondrial DNA is a common cause of Leigh's syndrome. Ann. Neurol. 34, 827-834 (1993). (Pubitemid 23357897)
14. Holt, I. J., Harding, A. E., Petty, R. K. & Morgan-Hughes, J. A. A new mitochondrial disease associated with mitochondrial DNA heteroplasmy. Am. J. Hum. Genet. 46, 428-433 (1990).
15. Elliott, H. R., Samuels, D. C., Eden, J. A., Relton, C. L. & Chinnery, P. F. Pathogenic mitochondrial DNA mutations are common in the general population. Am. J. Hum. Genet. 83, 254-260 (2008).
16. Stewart, J. B. et al. Strong purifying selection in transmission of mammalian mitochondrial DNA. PLoS Biol. 6, e10 (2008).
17. Prezant, T. R. et al. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nature Genet. 4, 289-294 (1993). (Pubitemid 23205179)
18. Raimundo, N. et al. Mitochondrial stress engages E2F1 apoptotic signaling to cause deafness. Cell 148, 716-726 (2012).
19. Gilkerson, R. W. et al. Mitochondrial autophagy in cells with mtDNA mutations results from synergistic loss of transmembrane potential and mTORC1 inhibition. Hum. Mol. Genet. 21, 978-990 (2012).
20. Gilkerson, R. W., Schon, E. A., Hernandez, E. & Davidson, M. M. Mitochondrial nucleoids maintain genetic autonomy but allow for functional complementation. J. Cell Biol. 181, 1117-1128 (2008). (Pubitemid 351915487)
21. Sgarbi, G. et al. Inefficient coupling between proton transport and ATP synthesis may be the pathogenic mechanism for NARP and Leigh syndrome resulting from the T8993G mutation in mtDNA. Biochem. J. 395, 493-500 (2006).
22. Holt, I. J., Harding, A. E. & Morgan-Hughes, J. A. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331, 717-719 (1988). (Pubitemid 18062238)
23. Lestienne, P. & Ponsot, G. Kearns-Sayre syndrome with muscle mitochondrial DNA deletion. Lancet 331, 885-886 (1988).
24. Damas, J. et al. Mitochondrial DNA deletions are associated with non-B DNA conformations. Nucleic Acids Res. 40, 7606-7621 (2012).
25. Kearns, T. P. & Sayre, G. P. Retinitis pigmentosa, external ophthalmophegia, and complete heart block: unusual syndrome with histologic study in one of two cases. AMA Arch. Ophthalmol. 60, 280-289 (1958).
26. Moraes, C. T. et al. Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N. Engl. J. Med. 320, 1293-1299 (1989). (Pubitemid 19140403)
27. Pearson, H. A. et al. A new syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction. J. Pediatr. 95, 976-984 (1979). (Pubitemid 10249785)
28. Nakase, H. et al. Transcription and translation of deleted mitochondrial genomes in Kearns-Sayre syndrome: implications for pathogenesis. Am. J. Hum. Genet. 46, 418-427 (1990).
29. Mita, S., Schmidt, B., Schon, E. A., DiMauro, S. & Bonilla, E. 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 (1989). (Pubitemid 20010456)
30. Moraes, C. T. et al. Molecular analysis of the muscle pathology associated with mitochondrial DNA deletions. Nature Genet. 1, 359-367 (1992).
31. Ashley, N. et al. Defects in maintenance of mitochondrial DNA are associated with intramitochondrial nucleotide imbalances. Hum. Mol. Genet. 16, 1400-1411 (2007). (Pubitemid 47055114)
32. Moraes, C. T. et al. Mitochondrial DNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases. Am. J. Hum. Genet. 48, 492-501 (1991). (Pubitemid 21903047)
33. Nishigaki, Y., Marti, R., Copeland, W. C. & Hirano, M. Site-specific somatic mitochondrial DNA point mutations in patients with thymidine phosphorylase deficiency. J. Clin. Invest. 111, 1913-1921 (2003). (Pubitemid 38057736)
34. Nishino, I., Spinazzola, A. & Hirano, M. Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 283, 689-692 (1999).
35. Kaukonen, J. et al. Role of adenine nucleotide translocator 1 in mtDNA maintenance. Science 289, 782-785 (2000). (Pubitemid 30650199)
36. Van Goethem, G., Dermaut, B., Lofgren, A., Martin, J. J. & Van Broeckhoven, C. Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nature Genet. 28, 211-212 (2001). (Pubitemid 32626018)
37. Spelbrink, J. N. et al. Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria. Nature Genet. 28, 223-231 (2001). (Pubitemid 32626024)
38. Naviaux, R. K. & Nguyen, K. V. POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. Ann. Neurol. 55, 706-712 (2004). (Pubitemid 38544331)
39. Moraes, C. T. et al. Phenotype-genotype correlations in skeletal muscle of patients with mtDNA deletions. Muscle Nerve 3, S150-S153 (1995).
40. Cortopassi, G. A., Shibata, D., Soong, N. W. & Arnheim, N. A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. Proc. Natl Acad. Sci. USA 89, 7370-7374 (1992).
41. Corral-Debrinski, M. et al. Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age. Nature Genet. 2, 324-329 (1992).
42. Meissner, C. et al. The 4977 bp deletion of mitochondrial DNA in human skeletal muscle, heart and different areas of the brain: a useful biomarker or more? Exp. Gerontol. 43, 645-652 (2008).
43. Pallotti, F., Chen, X., Bonilla, E. & Schon, E. A. Evidence that specific mtDNA point mutations may not accumulate in skeletal muscle during normal human aging. Am. J. Hum. Genet. 59, 591-602 (1996). (Pubitemid 26269037)
44. Simonetti, S., Chen, X., DiMauro, S. & Schon, E. A. Accumulation of deletions in human mitochondrial DNA during normal aging: analysis by quantitative PCR. Biochim. Biophys. Acta 1180, 113-122 (1992).
45. Oldfors, A. et al. Mitochondrial DNA deletions and cytochrome c oxidase deficiency in muscle fibres. J. Neurol. Sci. 110, 169-177 (1992).
46. Bodyak, N. D., Nekhaeva, E., Wei, J. Y. & Khrapko, K. Quantification and sequencing of somatic deleted mtDNA in single cells: evidence for partially duplicated mtDNA in aged human tissues. Hum. Mol. Genet. 10, 17-24 (2001). (Pubitemid 32051563)
47. Vu, T. H. et al. Analysis of mtDNA deletions in muscle by in situ hybridization. Muscle Nerve 23, 80-85 (2000). (Pubitemid 30013866)
48. Petruzzella, V. et al. Extremely high levels of mutant mtDNAs co-localize with cytochrome c oxidase-negative ragged-red fibers in patients harboring a point mutation at nt-3243. Hum. Mol. Genet. 3, 449-454 (1994). (Pubitemid 24083906)
49. Bua, E. et al. Mitochondrial DNA-deletion mutations accumulate intracellularly to detrimental levels in aged human skeletal muscle fibers. Am. J. Hum. Genet. 79, 469-480 (2006). (Pubitemid 44384256)
50. Schon, E. A. & Przedborski, S. Mitochondria: the next (neurode)generation. Neuron 70, 1033-1053 (2011).
51. Vives-Bauza, C. et al. Control of mitochondrial integrity in Parkinson's disease. Prog. Brain Res. 183, 99-113 (2010).
52. Narendra, D. P. & Youle, R. J. Targeting mitochondrial dysfunction: role for PINK1 and Parkin in mitochondrial quality control. Antioxid. Redox Signal. 14, 1929-1938 (2011).
53. Bender, A. et al. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nature Genet. 38, 515-517 (2006).
54. Kraytsberg, Y. et al. Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nature Genet. 38, 518-520 (2006).
55. Ekstrand, M. I. et al. Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons. Proc. Natl Acad. Sci. USA 104, 1325-1330 (2007). (Pubitemid 46184003)
56. De Coo, I. F. et al. A 4-base pair deletion in the mitochondrial cytochrome b gene associated with parkinsonism/MELAS overlap syndrome. Ann. Neurol. 45, 130-133 (1999). (Pubitemid 29036443)
57. Inoue, K. et al. Generation of mice with mitochondrial dysfunction by introducing mouse mtDNA carrying a deletion into zygotes. Nature Genet. 26, 176-181 (2000).
58. Tyynismaa, H. et al. Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice. Proc. Natl Acad. Sci. USA 102, 17687-17692 (2005). (Pubitemid 41803558)
59. Cann, R. L., Stoneking, M. & Wilson, A. C. Mitochondrial DNA and human evolution. Nature 325, 31-36 (1987). (Pubitemid 17059465)
60. Ruiz-Pesini, E., Mishmar, D., Brandon, M., Procaccio, V. & Wallace, D. C. Effects of purifying and adaptive selection on regional variation in human mtDNA. Science 303, 223-226 (2004). (Pubitemid 38057570)
61. Amo, T. & Brand, M. D. Were inefficient mitochondrial haplogroups selected during migrations of modern humans? A test using modular kinetic analysis of coupling in mitochondria from cybrid cell lines. Biochem. J. 404, 345-351 (2007). (Pubitemid 46849606)
62. Saxena, R. et al. Comprehensive association testing of common mitochondrial DNA variation in metabolic disease. Am. J. Hum. Genet. 79, 54-61 (2006). (Pubitemid 43927376)
63. Kadowaki, T. et al. A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA. N. Engl. J. Med. 330, 962-968 (1994). (Pubitemid 24103594)
64. Bitner-Glindzicz, M. et al. Prevalence of mitochondrial 1555A→G mutation in European children. N. Engl. J. Med. 360, 640-642 (2009).
65. Vandebona, H. et al. Prevalence of mitochondrial 1555A→G mutation in adults of European descent. N. Engl. J. Med. 360, 642-644 (2009).
66. Andreu, A. L. et al. Exercise intolerance due to mutations in the cytochrome b gene of mitochondrial DNA. N. Engl. J. Med. 341, 1037-1044 (1999). (Pubitemid 29451799)
67. Elson, J. L., Majamaa, K., Howell, N. & Chinnery, P. F. Associating mitochondrial DNA variation with complex traits. Am. J. Hum. Genet. 80, 378-382; author reply 382-383 (2007). (Pubitemid 46175686)
68. Carelli, V. et al. Haplogroup effects and recombination of mitochondrial DNA: novel clues from the analysis of Leber hereditary optic neuropathy pedigrees. Am. J. Hum. Genet. 78, 564-574 (2006).
69. Hudson, G. et al. Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background. Am. J. Hum. Genet. 81, 228-233 (2007). (Pubitemid 47236071)
70. Ghelli, A. et al. The background of mitochondrial DNA haplogroup J increases the sensitivity of Leber's hereditary optic neuropathy cells to 2,5-hexanedione toxicity. PLoS ONE 4, e7922 (2009).
71. Anderson, C. D. et al. Common mitochondrial sequence variants in ischemic stroke. Ann. Neurol. 69, 471-480 (2011).
72. Arning, L. et al. Mitochondrial haplogroup H correlates with ATP levels and age at onset in Huntington disease. J. Mol. Med. 88, 431-436 (2010).
73. Ingram, C. J. et al. Analysis of European case-control studies suggests that common inherited variation in mitochondrial DNA is not involved in susceptibility to amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 13, 341-346 (2012).
74. Hiona, A. & Leeuwenburgh, C. The role of mitochondrial DNA mutations in aging and sarcopenia: implications for the mitochondrial vicious cycle theory of aging. Exp. Gerontol. 43, 24-33 (2008). (Pubitemid 350245432)
75. Khusnutdinova, E. et al. A mitochondrial etiology of neurodegenerative diseases: evidence from Parkinson's disease. Ann. NY Acad. Sci.1147, 1-20 (2008).
76. Mancuso, M., Filosto, M., Orsucci, D. & Siciliano, G. Mitochondrial DNA sequence variation and neurodegeneration. Hum. Genom. 3, 71-78 (2008).
77. Nishigaki, Y., Fuku, N. & Tanaka, M. Mitochondrial haplogroups associated with lifestyle-related diseases and longevity in the Japanese population. Geriatr. Gerontol. Int. 10, S221-S235 (2010).
78. Rose, G. et al. No evidence of association between frontotemporal dementia and major European mtDNA haplogroups. Eur. J. Neurol. 15, 1006-1008 (2008).
79. SanGiovanni, J. P. et al. Mitochondrial DNA variants of respiratory complex I that uniquely characterize haplogroup T2 are associated with increased risk of age-related macular degeneration. PLoS ONE 4, e5508 (2009).
80. Sanchez-Ferrero, E. et al. Mitochondrial DNA polymorphisms/haplogroups in hereditary spastic paraplegia. J. Neurol. 259, 246-250.
81. Santoro, A. et al. Evidence for sub-haplogroup h5 of mitochondrial DNA as a risk factor for late onset Alzheimer's disease. PLoS ONE 5, e12037 (2012).
82. Sequeira, A. et al. Mitochondrial mutations and polymorphisms in psychiatric disorders. Front. Genet. 3, 103 (2012).
83. Tranah, G. J. Mitochondrial-nuclear epistasis: implications for human aging and longevity. Ageing Res. Rev. 10, 238-252 (2012).
84. McRae, A. F., Byrne, E. M., Zhao, Z. Z., Montgomery, G. W. & Visscher, P. M. Power and SNP tagging in whole mitochondrial genome association studies. Genome Res. 18, 911-917 (2008). (Pubitemid 351793063)
85. Battersby, B. J. & Shoubridge, E. A. Selection of a mtDNA sequence variant in hepatocytes of heteroplasmic mice is not due to differences in respiratory chain function or efficiency of replication. Hum. Mol. Genet. 10, 2469-2479 (2001). (Pubitemid 33094997)
86. Warburg, O., Wind, F. & Negelein, E. The metabolism of tumors in the body. J. Gen. Physiol. 8, 519-530 (1927).
87. Polyak, K. et al. Somatic mutations of the mitochondrial genome in human colorectal tumours. Nature Genet. 20, 291-293 (1998). (Pubitemid 28507677)
88. Yu, M. Generation, function and diagnostic value of mitochondrial DNA copy number alterations in human cancers. Life Sci. 89, 65-71 (2011).
89. Melnick, P. J. Enzyme patterns of tumors demonstrated histochemically in cryostat sections. Ann. NY Acad. Sci.125, 689-715 (1965).
90. Pelicano, H. et al. Mitochondrial respiration defects in cancer cells cause activation of Akt survival pathway through a redox-mediated mechanism. J. Cell Biol. 175, 913-923 (2006). (Pubitemid 44969197)
91. Yu, M. et al. Reduced mitochondrial DNA copy number is correlated with tumor progression and prognosis in Chinese breast cancer patients. IUBMB Life 59, 450-457 (2007). (Pubitemid 47124001)
92. Bai, R. K. et al. Mitochondrial DNA content varies with pathological characteristics of breast cancer. J. Oncol. 2011, 496189 (2011).
93. King, M. P., Koga, Y., Davidson, M. & Schon, E. A. Defects in mitochondrial protein synthesis and respiratory chain activity segregate with the tRNALeu(UUR) mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. Mol. Cell. Biol. 12, 480-490 (1992).
94. Miller, R. W. Dihydroorotate-quinone reductase of Neurospora crassa mitochondria. Arch. Biochem. Biophys. 146, 256-270 (1971).
95. Hayashi, J., Takemitsu, M. & Nonaka, I. Recovery of the missing tumorigenicity in mitochondrial DNA-less HeLa cells by introduction of mitochondrial DNA from normal human cells. Somat. Cell. Mol. Genet. 18, 123-129 (1992).
96. Morais, R. et al. Tumor-forming ability in athymic nude mice of human cell lines devoid of mitochondrial DNA. Cancer Res. 54, 3889-3896 (1994). (Pubitemid 24241212)
97. Peters, G. J. et al. In vivo inhibition of the pyrimidine de novo enzyme dihydroorotic acid dehydrogenase by brequinar sodium (DUP-785; NSC 368390) in mice and patients. Cancer Res. 50, 4644-4649 (1990). (Pubitemid 20230407)
98. Mourier, T., Hansen, A. J., Willerslev, E. & Arctander, P. The Human Genome Project reveals a continuous transfer of large mitochondrial fragments to the nucleus. Mol. Biol. Evol. 18, 1833-1837 (2001). (Pubitemid 32776934)
99. Ramos, A. et al. Nuclear insertions of mitochondrial origin: database updating and usefulness in cancer studies. Mitochondrion 11, 946-953 (2011).
100. Hazkani-Covo, E., Zeller, R. M. & Martin, W. Molecular poltergeists: mitochondrial DNA copies (numts) in sequenced nuclear genomes. PLoS Genet. 6, e1000834 (2010).
101. Lang, M. et al. Polymorphic Numts trace human population relationships. Hum. Genet. 131, 757-771 (2012).
102. Wang, D., Lloyd, A. H. & Timmis, J. N. Environmental stress increases the entry of cytoplasmic organellar DNA into the nucleus in plants. Proc. Natl Acad. Sci. USA 109, 2444-2448 (2012).
103. Cheng, X. & Ivessa, A. S. The migration of mitochondrial DNA fragments to the nucleus affects the chronological aging process of Saccharomyces cerevisiae. Aging Cell 9, 919-923 (2010).
104. Caro, P. et al. Mitochondrial DNA sequences are present inside nuclear DNA in rat tissues and increase with age. Mitochondrion 10, 479-486 (2010).
105. Goldin, E. et al. Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucolipidosis IV. Hum. Mutat. 24, 460-465 (2004). (Pubitemid 39664599)
106. Turner, C. et al. Human genetic disease caused by de novo mitochondrial-nuclear DNA transfer. Hum. Genet. 112, 303-309 (2003). (Pubitemid 36869088)
107. Willett-Brozick, J. E., Savul, S. A., Richey, L. E. & Baysal, B. E. Germ line insertion of mtDNA at the breakpoint junction of a reciprocal constitutional translocation. Hum. Genet. 109, 216-223 (2001). (Pubitemid 32825563)
108. Storlazzi, C. T. et al. Gene amplification as double minutes or homogeneously staining regions in solid tumors: origin and structure. Genome Res. 20, 1198-1206 (2010).
109. Valsesia, A. et al. Network-guided analysis of genes with altered somatic copy number and gene expression reveals pathways commonly perturbed in metastatic melanoma. PLoS ONE 6, e18369 (2011).
110. Hirano, T. et al. Co-localization of mitochondrial and double minute DNA in the nuclei of HL-60 cells but not normal cells. Mutat. Res. 425, 195-204 (1999). (Pubitemid 29182653)
111. Lee, J. H., Ryu, T. Y., Cho, C. H. & Kim, D. K. Different characteristics of mitochondrial microsatellite instability between uterine leiomyomas and leiomyosarcomas. Pathol. Oncol. Res. 17, 201-205 (2011).
112. Ellinger, J. et al. Circulating mitochondrial DNA in serum: A universal diagnostic biomarker for patients with urological malignancies. Urol. Oncol. 30, 509-515 (2012).
113. Kiebish, M. A. & Seyfried, T. N. Absence of pathogenic mitochondrial DNA mutations in mouse brain tumors. BMC Cancer 5, 102 (2005).
114. Ericson, N. G. et al. Decreased mitochondrial DNA mutagenesis in human colorectal cancer. PLoS Genet. 8, e1002689 (2012).
115. Chinnery, P. F., Samuels, D. C., Elson, J. & Turnbull, D. M. Accumulation of mitochondrial DNA mutations in ageing, cancer, and mitochondrial disease: is there a common mechanism? Lancet 360, 1323-1325 (2002). (Pubitemid 35284628)
116. Parr, R. L. et al. The pseudo-mitochondrial genome influences mistakes in heteroplasmy interpretation. BMC Genomics 7, 185 (2006).
117. Maki, J. et al. Mitochondrial genome deletion aids in the identification of false-and true-negative prostate needle core biopsy specimens. Am. J. Clin. Pathol. 129, 57-66 (2008). (Pubitemid 352038594)
118. Parr, R. L. et al. Somatic mitochondrial DNA mutations in prostate cancer and normal appearing adjacent glands in comparison to age-matched prostate samples without malignant histology. J. Mol. Diagn. 8, 312-319 (2006). (Pubitemid 44063807)
119. DiMauro, S. & Andreu, A. L. Mutations in mtDNA: are we scraping the bottom of the barrel? Brain Pathol. 10, 431-441 (2000). (Pubitemid 30431296)
120. Giordano, C. et al. Oestrogens ameliorate mitochondrial dysfunction in Leber's hereditary optic neuropathy. Brain 134, 220-234 (2011).
121. Kaufmann, P. et al. Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. Neurology 77, 1965-1971 (2011).
122. Tay, S. H. et al. Aortic rupture in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes. Arch. Neurol. 63, 281-283 (2006). (Pubitemid 43261742)
123. Chong, P. S., Vucic, S., Hedley-Whyte, E. T., Dreyer, M. & Cros, D. Multiple symmetric lipomatosis (Madelung's disease) caused by the MERRF (A8344G) mutation: a report of two cases and review of the literature. J. Clin. Neuromuscul. Dis. 5, 1-7 (2003). (Pubitemid 38404431)
124. Suzuki, T., Nagao, A. & Suzuki, T. Human mitochondrial diseases caused by lack of taurine modification in mitochondrial tRNAs. Wiley Interdiscip. Rev. RNA 2, 376-386 (2011).
125. Hasegawa, H., Matsuoka, T., Goto, Y. & Nonaka, I. Cytochrome c oxidase activity is deficient in blood vessels of patients with myoclonus epilepsy with ragged-red fibers. Acta Neuropathol. 85, 280-284 (1993). (Pubitemid 23081176)
126. Naini, A. et al. Hypocitrullinemia in patients with MELAS: an insight into the "MELAS paradox". J. Neurol. Sci. 229-230, 187-193 (2005). (Pubitemid 40347254)
127. Shiva, S., Brookes, P. S., Patel, R. P., Anderson, P. G. & Darley-Usmar, V. M. Nitric oxide partitioning into mitochondrial membranes and the control of respiration at cytochrome c oxidase. Proc. Natl Acad. Sci. USA 98, 7212-7217 (2001). (Pubitemid 32567928)
128. Torres, J., Darley-Usmar, V. & Wilson, M. T. Inhibition of cytochrome c oxidase in turnover by nitric oxide: mechanism and implications for control of respiration. Biochem. J. 312, 169-173 (1995).
129. Rodriguez-Juarez, F., Aguirre, E. & Cadenas, S. Relative sensitivity of soluble guanylate cyclase and mitochondrial respiration to endogenous nitric oxide at physiological oxygen concentration. Biochem. J. 405, 223-231 (2007). (Pubitemid 47075157)
130. Koga, Y. et al. l-arginine improves the symptoms of strokelike episodes in MELAS. Neurology 64, 710-712 (2005). (Pubitemid 40261903)
131. Horvath, R. et al. Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy. Brain 132, 3165-3174 (2009).
132. Uusimaa, J. et al. Reversible infantile respiratory chain deficiency is a unique, genetically heterogenous mitochondrial disease. J. Med. Genet. 48, 660-668 (2011).
133. Umeda, N. et al. Mitochondria-specific RNA-modifying enzymes responsible for the biosynthesis of the wobble base in mitochondrial tRNAs. Implications for the molecular pathogenesis of human mitochondrial diseases. J. Biol. Chem. 280, 1613-1624 (2005).
134. Yan, Q. et al. Human TRMU encoding the mitochondrial 5-methylaminomethyl- 2-thiouridylate-methyltransferase is a putative nuclear modifier gene for the phenotypic expression of the deafness-associated 12S rRNA mutations. Biochem. Biophys. Res. Commun. 342, 1130-1136 (2006).
135. King, M. P. & Attardi, G. Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science 246, 500-503 (1989). (Pubitemid 19273941)
136. King, M. P. & Attardi, G. Isolation of human cell lines lacking mitochondrial DNA. Methods Enzymol. 264, 304-313 (1996). (Pubitemid 26089319)
137. Engel, W. K. & Cunningham, G. G. Rapid examination of muscle tissue. An improved trichrome method for fresh-frozen biopsy sections. Neurology 13, 919-923 (1963).
138. Bonilla, E. et al. New morphological approaches to the study of mitochondrial encephalomyopathies. Brain Pathol. 2, 113-119 (1992).
139. Quinzii, C. M. et al. Reactive oxygen species, oxidative stress, and cell death correlate with level of CoQ10 deficiency. FASEB J. 24, 3733-3743 (2010).
140. Loveland, B., Wang, C. R., Yonekawa, H., Hermel, E. & Lindahl, K. F. Maternally transmitted histocompatibility antigen of mice: a hydrophobic peptide of a mitochondrially encoded protein. Cell 60, 971-980 (1990).
141. Gogvadze, V., Orrenius, S. & Zhivotovsky, B. Mitochondria in cancer cells: what is so special about them? Trends Cell Biol. 18, 165-173 (2008).
142. Madan, E. et al. Regulation of glucose metabolism by p53: emerging new roles for the tumor suppressor. Oncotarget 2, 948-957 (2011).
143. van Nederveen, F. H. et al. An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis. Lancet Oncol. 10, 764-771 (2009).
144. Tomlinson, I. P. et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nature Genet. 30, 406-410 (2002).
145. Selak, M. A. et al. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase. Cancer Cell 7, 77-85 (2005). (Pubitemid 40126384)
146. Lemasters, J. J. & Holmuhamedov, E. Voltage-dependent anion channel (VDAC) as mitochondrial governator-thinking outside the box. Biochim. Biophys. Acta 1762, 181-190 (2006). (Pubitemid 43006024)
147. Majewski, N., Nogueira, V., Robey, R. B. & Hay, N. Akt inhibits apoptosis downstream of BID cleavage via a glucose-dependent mechanism involving mitochondrial hexokinases. Mol. Cell. Biol. 24, 730-740 (2004). (Pubitemid 38057924)
148. Jain, M. et al. Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science 336, 1040-1044 (2012).
149. DiMauro, S., Hirano, M. & Schon, E. A. Approaches to the treatment of mitochondrial diseases. Muscle Nerve 34, 265-283 (2006). (Pubitemid 44300157)