Mitochondria in Hematology

  • Stefanie Zanssen

The “mitochondrial clock” limits human life span by decreasing energy supply in the aged. If other mechanisms to limit human life span, such as severe infections or cancer, are eliminated, even the “healthy” aging rarely live beyond 100 years owing to mitochondrial degeneration, one of the three bases of aging. This refers to a substantial higher mutation rate of the mitochondrial genome than the nuclear genome (6 × 10−11 mutations per site per cell division), which is caused by a weaker mitochondrial repair system (Wallace1999). The estimated mutation rate of the mitochondrial genome from pedigree-derived data, for somatic mutations, for substitution rates in cultured cells, and for stem cells is strikingly similar and corresponds to 1.10 mutations per site per million years (Taylor et al.2003).

In fetal life the mutation load of the mitochondrial genome is very low, approximately 0.02%, but increases steadily over human life and aged people in their nineties may end up with 5–10%...


Acute Myeloid Leukemia Chronic Lymphocytic Leukemia Mitochondrial Genome Chronic Lymphocytic Leukemia Patient Mitochondrial Haplotype 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Amo T, Brandt MD. 2007;Were effecient mitochondrial haplogroups selected during migration of modern humans? A test using modular kinetic analysis of coupling in mitochondria from cybrid cell lines. Biochem J 404:345–351PubMedGoogle Scholar
  2. Aul C, Gattermann N, Schneider W. 1992;Age-related incidence and other epidemiological aspects of myelodysplastic syndromes. Br J Haematol 82:358–367PubMedGoogle Scholar
  3. Baysal BE. 2003;On the association of succinate dehydrogenase mutations with hereditary paraganglioma. Trends Endocrinol Metab 14:453–459.PubMedGoogle Scholar
  4. Baysal BE, Ferrell RE, Willett-Brozick JE, et al. 2000;Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287:848–851.PubMedGoogle Scholar
  5. Beckman JS, and Koppenol WH. 1996;Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271:C1424–1437.PubMedGoogle Scholar
  6. Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, Taylor RW, Turnbull DM. 2006;High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 38(5):515–517.PubMedGoogle Scholar
  7. Berger G, Hunault-Berger M, Rachieru P, Fontenay-Roupie M, Baranger L, Ifrah N, Zandecki M. 2001;Increased apoptosis in mononucleated cells but not CD34+. cells in blastic forms of myelodysplastic syndromes The Hematol J 2:87–96Google Scholar
  8. Bessis M. Living blood cells and their ultrastructure. 1973. Berlin: Springer.Google Scholar
  9. Boultwood J, Fidler C, Mills KI, Frodsham PM, Kusec R, Gaiger A, Gale RE, Linch DC, Littlewood TJ, Moss PAH, Wainscoat JS. 1996;Amplification of mitochondrial DNA in acute myeloid leukaemia. Br J Haematol 95:426–431PubMedGoogle Scholar
  10. Brierley EJ, Johnson MA, Lightowlers RN, James OFW, Turnbull DM. 1998;Role of mitochondrial DNA mutations in human aging: implications for the central nervous system and muscle. Ann Neurol 43:217–223PubMedGoogle Scholar
  11. Bröker S, Meunier B, Rich P, Gattermann N, Hofhaus G. 1998;mtDNA mutations associated with sideroblastic anaemia cause a defect of mitochondrial cytochrome c oxidase. Eur J Biochem 258:132–138PubMedGoogle Scholar
  12. Brown MD, Trounce IA, Jun AS, Allen JC, Wallace DC. 2000;Functional analysis of lymphoblast and cybrid mitochondria containing the 3460, 11778, or 14484 Leber’s hereditary optic neuropathy mitochondrial DNA mutation. J Biol Chem 275:39831–39836.PubMedGoogle Scholar
  13. Buttgereit F, Brand MD. 1995;A hierarchy of ATP-consuming processes in mammalian cells. Biochem J 312:163–167PubMedGoogle Scholar
  14. Canter JA, Kallianpur AR, Parl FF, Millikan RC. 2005;Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Res 65(17):8028–8033.PubMedGoogle Scholar
  15. Carew JS, Zhou Y, Alibar M, Carew JD, Keating MJ, Huang P. 2003;Mitochondrial DNA mutations in primary leukemia cells after chemotherapy: clinical significance and therapeutic implications. Leukemia 17:1437–1447PubMedGoogle Scholar
  16. Casas KA, Bykhovskaya Y, Mengesha E, Wang D, Yang H, Taylor K, Inbal A, Fischel-Ghodsian N. 2004;Gene responsible for mitochondrial myopathy and sideroblastic anemia (MSA) maps to chromosome 12q24.33. Am J Med Genet 127A:44–49PubMedGoogle Scholar
  17. Casas KA, Fischel-Ghodsian N. 2004;Mitochondrial myopathy and sideroblastic anemia. Am J Med Genet 125A:201–204PubMedGoogle Scholar
  18. Chalmers RM and Schapira AH. 1999;Clinical, biochemical and molecular genetic features of Leber’s hereditary optic neuropathy. Biochim Biophys Acta 1410:147–158.Google Scholar
  19. Chinnery PF, Samuels DC. 1999;Relaxed replication of mtDNA: a model with implications for the expression of disease. Am J Hum Genet 64:1158–1165PubMedGoogle Scholar
  20. Chinnery PF, Samuels DC, Elson JL, Turnbull DM. 2002;Accumulation of mitochondrial DNA mutations in ageing, cancer, and mitochondrial disease: is there a common mechanism? Lancet 360:1323–1325PubMedGoogle Scholar
  21. Christiansen G, Christiansen C, Zeuthen J. 1983;Complex forms of mitochondrial DNA in human B cells transformed by Epstein–Barr virus. J Cancer Res Clin Oncol 105:13–19PubMedGoogle Scholar
  22. Ciafaloni E, Ricci E, Shanske S, Moraes CT, Silvestri G, Hirano M, Simonetti S, Angelini C, Donati A, Garcia C, Martinuzzi A, Mosewich R, Servidei S, Zammarchi E, Bonilla E, DeVivo DC, Rowland LP, Schon EA, DiMauro S. 1992;MELAS: clinical features, biochemistry, and molecular genetics. Ann Neurol 31:391–398PubMedGoogle Scholar
  23. Clayton DA, Smith CA. 1975;Complex mitochondrial DNA. Int Rev Exp Pathol 14:1–67PubMedGoogle Scholar
  24. Clayton DA, Vinograd J. 1967;Circular dimer and catenate forms of mitochondrial DNA in human leukaemic leukocytes. Nature 216:652–657PubMedGoogle Scholar
  25. Clayton DA, Vinograd J. 1969;Complex mitochondrial DNA in leukemic and normal human myeloid cells. Proc Natl Acad Sci USA 62:1077–1084PubMedGoogle Scholar
  26. Coller HA, Khrapko K, Bodyak ND, Nekhaeva E, Herrero-Jimenez P, Thilly WG. 2001;High frequency of homoplasmic mitochondrial DNA mutations in human tumors can be explained without selection. Nat Genet 28:147–150PubMedGoogle Scholar
  27. Coskun PE, Ruiz-Pesini E, Wallace DC. 2003;Control region mtDNA variants: Longevity, climatic adaptation, and a forensic conundrum. Proc Natl Acad Sci USA 100:2174–2176PubMedGoogle Scholar
  28. Crisan D. 2000;Molecular mechanisms in myelodysplastic syndromes and implications for evolution to acute leukemias. Clin Lab Med 20:49–69, viiiPubMedGoogle Scholar
  29. Danielson SR, Wong A, Carelli V, Martinuzzi A, Schapira AH, Cortopassi GA. 2002;Cells bearing mutations causing Leber’s hereditary optic neuropathy are sensitized to Fas-Induced apoptosis. J Biol Chem 277:5810–5815.PubMedGoogle Scholar
  30. de Grey AD. 1997;A proposed refinement of the mitochondrial free radical theory of ageing. Bioessays 19:161–166PubMedGoogle Scholar
  31. Dick JE, Lapidot T. (2005) Biology of normal and acute myeloid leukemia stem cells. Int J Hematol 82(5):389–396. Review.PubMedGoogle Scholar
  32. DiMauro S, Schon EA. 2003;Mitochondrial respiratory-chain diseases. N Engl J Med 348:2656–2668.PubMedGoogle Scholar
  33. Donnellan R, Chetty R. 1998;Cyclin D1 and human neoplasia (). Mol Pathol 51(1):1–7.ReviewPubMedGoogle Scholar
  34. Elson JL, Samuels DC, Turnbull DM, Chinnery PF. 2001;Random intracellular drift explains the clonal expansion of mitochondrial mutations with age. Am J Hum Genet 68:802–806PubMedGoogle Scholar
  35. Elson JL, Turnbull JM, Taylor RW. 2007;Testing the adaptive selection of mitochondrial haplogroups: an experimental bioenergetics approach. Biochem J 404:e3–e35PubMedGoogle Scholar
  36. Eng C, Kiuru M, Fernandez MJ, et al. 2003;A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat Rev Cancer 3:193–202.PubMedGoogle Scholar
  37. Firkin FC, Clark-Walker GD. 1979;Abnormal mitochondrial DNA in acute leukemia and lymphoma. Br J Haematol 43:201–206PubMedGoogle Scholar
  38. Fliss MS, Usadel H, Cabalero OL, Wu L, Buta M, Eleff SM, Jen J, Sidransky D. 2000;Facile detection of mitochondrial DNA mutations in tumors and bodily fluids. Science 287:2017–2019PubMedGoogle Scholar
  39. Gattermann N. 2000;From sideroblastic anemia to the role of mitochondrial DNA mutations in myelodysplastic syndromes. Leuk Res 24:141–151.PubMedGoogle Scholar
  40. Gattermann N, Aul C. 1997;Mitochondrial DNA amplification in AML: a hypothesis. Br J Haematol 97:242.PubMedGoogle Scholar
  41. Gattermann N, Aul C, Schneider W. 1990;Two types of acquired idiopathic sideroblastic anaemia (AISA). Br J Haematol 74:45–52PubMedGoogle Scholar
  42. Gattermann N, Berneburg M, Heinisch J, Aul C, Schneider W. 1995;Detection of the ageing-associated 5-Kb deletion of mitochondrial DNA in blood and bone marrow of hematologically normal adults. Absence of the deletion in clonal bone marrow disorders. Leukemia 9:1704–1710PubMedGoogle Scholar
  43. Gattermann N, Retzlaff S, Wang Y-L, Berneburg M, Heinisch J, Wlaschek M, Aul C, Schneider W. 1996;A heteroplasmic point mutation of mitochondrial tRNALeu(CUN). in non-lymphoid cell lineages from a patient with acquired idiopathic sideroblastic anaemia Br J Haematol 93:845–855PubMedGoogle Scholar
  44. Gattermann N, Retzlaff S, Wang Y-L, Hofhaus G, Heinisch J, Aul C, Schneider W. 1997;Heteroplasmic point mutations of mitochondrial DNA affecting subunit I of cytochrome c oxidase in two patients with acquired idiopathic sideroblastic anemia. Blood 90:4961–4972PubMedGoogle Scholar
  45. Geiger H, van Zant G. 2002;The aging of lympho-hematopoietic stem cells. Nat Immunol 3:329–333PubMedGoogle Scholar
  46. Germing U, Gattermann N, Aivado M, Hildebrandt B, Aul C. 2000;Two types of acquired idiopathic sideroblastic anaemia (AISA): a time-tested distinction. Br J Haematol 108:724–728PubMedGoogle Scholar
  47. Goto Y-I, Horai S, Matsuoka T, Koga Y, Nihei K, Kobayashi M, Nonaka I. 1991;Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): a correlative study of the clinical features and mitochondrial DNA mutation. Neurology 42:545–550Google Scholar
  48. Gutteridge JM. 1989;Iron and oxygen: a biologically damaging mixture. Acta Paediatr Scand Suppl 361:78–85PubMedGoogle Scholar
  49. Habano W, Nakamura S, Sugai T. 1998;Microsatellite instability in the mitochondrial DNA of colorectal carcinomas: evidence for mismatch repair systems in mitochondrial genome. Oncogene 17:1931–1937PubMedGoogle Scholar
  50. Haddad JJ. 2002;Redox regulation of pro-inflammatory cytokines and IkappaB-alpha/NF-kappaB nuclear translocation and activation. Biochem Biophys Res Commun 296:847–856PubMedGoogle Scholar
  51. Harris NL, Jaffe ES, Diebold J, et al. 1999;World Health Organisation classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the clinical advisory committee meeting—Airlie House, Virginia. J Clin Oncol 17:3835–3849PubMedGoogle Scholar
  52. Hatfill S, Kirby R. 1994;Abnormal mitochondrial DNA length polymorphism in patients with the myelodysplastic syndrome. Blood 84:314aGoogle Scholar
  53. He L, Luo L, Proctor SJ, Middleton PG, Blakely EL, Taylor RW. 2003;Turnbull DM. Somatic mitochondrial DNA mutations in adult-onset leukaemia. Leukemia 17:2487–2491.PubMedGoogle Scholar
  54. Hofhaus G, Gattermann N. 1999;Mitochondria harbouring mutant mtDNA – a cuckoo in the nest? Biol Chem 380:871–877PubMedGoogle Scholar
  55. Hofhaus G, Johns DR, Hurko O, Attardi G, Chomyn A. 1996;Respiration and growth defects in transmitochondrial cell lines carrying the 11778 mutation associated with Leber’s hereditary optic neuropathy. J Biol Chem 271:13155–13161.PubMedGoogle Scholar
  56. Holme E, Tulinius MH, Larsson N-G, Oldfors A. 1995;Inheritance and expression of mitochondrial DNA point mutations. Biochim Biophys Acta 1271:249–252PubMedGoogle Scholar
  57. Horton TM, Petros JA, Heddi A, Shoffner J, Kaufman AE, et al. 1996;Novel mitochondrial DNA deletion found in a renal cell carcinoma. Genes Chromosomes Cancer 15:95–101.PubMedGoogle Scholar
  58. Howell N. 1998;Leber hereditary optic neuropathy: respiratory chain dysfunction and degeneration of the optic nerve. Vision Res 38:1495–1504PubMedGoogle Scholar
  59. Inbal A, Avissar NSM, Kuritzky A, Schejter A, Ben-David E, Shanske S, Garty B-Z. 1995;Myopathy, lactic acidosis, and sideroblastic anemia: A new syndrome. Am J Med Genet 55:371–378Google Scholar
  60. Ivanova R, Lepage V, Loste MN, Schachter F, Wijnen E, Busson M, Cayuela JM, Sigaux F, Charron D. 1998;Mitochondrial DNA sequence variation in human leukemic cells. Int J Cancer 76:495–498PubMedGoogle Scholar
  61. Jeronimo C, Nomoto S, Caballero OL, Usadel H, Henrique R, Varzim G, Oliveira J, Lopes C, Fliss MS, Sidransky D. 2001;Mitochondrial mutations in early stage prostate cancer and bodily fluids. Oncogene 20:5195–5198PubMedGoogle Scholar
  62. Johns DR, Neufeld MJ. 1993;Pitfalls in the molecular genetic diagnosis of Leber hereditary optic neuropathy (LHON). Am J Hum Genet 53:916–920.PubMedGoogle Scholar
  63. Jones JB, Song JJ, Hempen PM, Parmigiani G, Hruban RH, Kern SE. 2001;Detection of mitochondrial DNA mutations in pancreatic cancer offers a ’mass”-ive advantage over detection of nuclear DNA mutations. Cancer Res 61:1299–1304PubMedGoogle Scholar
  64. Kraytsberg Y, Nekhaeva E, Bodyak ND, Khrapko K. 2003;Mutation and intracellular clonal expansion of mitochondrial genomes: two synergistic components of the aging process? Mech Ageing Dev 124:49–53PubMedGoogle Scholar
  65. Kroemer G, Reed JC. 2000;Mitochondrial control of cell death. Nat Med 6:513–519PubMedGoogle Scholar
  66. Larsson NG, Holme E, Kristiansson B, Oldfors A, Tulinius M. 1991;Progressive increase of the mutated mitochondrial DNA fraction in Kearns-Sayre syndrome. Pediatr Res 28:131–133Google Scholar
  67. Liang Y, Van Zant G, Szilvassy SJ. 2005;Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood 106:1479–1487PubMedGoogle Scholar
  68. Linnartz B, Anglmayer R, Zanssen S. 2004;Comprehensive scanning of somatic mitochondrial DNA alterations in acute leukemia developing from myelodysplastic syndromes. Cancer Res 64:1966–1971.PubMedGoogle Scholar
  69. Liu VW, Shi HH, Cheung AN, Chiu PM, Leung TW, Nagley P, Wong LC, Ngan HY. 2001;High incidence of somatic mitochondrial DNA mutations in human ovarian carcinomas. Cancer Res 61:5998–6001.PubMedGoogle Scholar
  70. Liu SL, Lin X, Shi DY, Cheng J, Wu CQ, Zhang YD. 2002;Reactive oxygen species stimulate human hepatoma cell proliferation via cross-talk between PI3K/PKB and JNK signaling pathways. Arch Biochem Biophys 406:173–182PubMedGoogle Scholar
  71. Luft R. 1994;The development of mitochondrial medicine. Proc Natl Acad Sci USA 91:8731–8738.PubMedGoogle Scholar
  72. Marley SB, Lewis JL, Davidson RJ, Roberts IAG, Dokal I, Goldman JM, Gordon MY. 1999;Evidence for a continuous decline in haematopoietic cell function from birth: application to evaluating bone marrow failure in children. Br J Haematol 106:162–166PubMedGoogle Scholar
  73. McShane MA, Hammans SR, Sweeney M, Holt IJ, Beattie TJ, Brett EM, Harding AE. 1991;Pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtDNA. Am J Hum Genet 48:39–42PubMedGoogle Scholar
  74. Miguel A, Hernández-Yago J, Knecht E, Renau-Piqueras J. 1982;A comparative study of complex mitochondrial DNA in human lymphocytes transformed by Epstein–Barr virus and PHA. Acta Haematologica 68:96–104PubMedGoogle Scholar
  75. Modica-Napolitano JS, Kulawiec M, Singh KK. 2007;Mitochondria and human cancer (). Curr Mol Med 7(1):121–31.ReviewPubMedGoogle Scholar
  76. Morrison SJ, Wandycz AM, Akashi K, Globerson A, Weissman IL. 1996;The aging of hematopoietic stem cells. Nat Med 2:1011–1016PubMedGoogle Scholar
  77. Muller-Hocker J. 1992;Random cytochrome-C-oxidase deficiency of oxyphil cell nodules in the parathyroid gland. A mitochondrial cytopathy related to cell ageing? Pathol Res Pract 188:701–706.PubMedGoogle Scholar
  78. Murdock DG, Christiacos NC, Wallace DC. 2000;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 28:4350–4355PubMedGoogle Scholar
  79. Nekhaeva E, Bodyak ND, Kraytsberg Y, McGrath SB, Van Orsouw NJ, Pluzhnikov A, Wei JY, Vijg J, Khrapko K. 2002;Clonally expanded mtDNA point mutations are abundant in individual cells of human tissues. Proc Natl Acad Sci USA 99:5521–5526PubMedGoogle Scholar
  80. Nelson I, Bonne G, Degoul F, Marsac C, Ponsot G, Lestienne P. 1992;Kearns–Sayre syndrome with sideroblastic anemia: molecular investigations. Neuropediatrics 23:199–205PubMedGoogle Scholar
  81. Nikoselainen E, Asola M, Kalimo H, Savontaus ML, Majander A. 1992;Benzodiazepine sensititvity in Leber’s hereditary optic neuropathy (letter). Lancet 340:1223–1224Google Scholar
  82. Okochi O, Hibi K, Uemura T, Inoue S, Takeda S, Kaneko T, Nakao A. 2002;Detection of mitochondrial DNA alterations in the serum of hepatocellular carcinoma patients. Clin Cancer Res 8:2875–2878PubMedGoogle Scholar
  83. Parker JE, Fishlock KL, Mijovic J, Czepulkowski B, Pagliuca A, Mufti GJ. 1998;‘Low-risk’ myelodysplastic syndrome is associated with excessive apoptosis and an increased ratio of pro- versus anti-apoptotic bcl-2-related proteins. Br J Haematol 103:1075–1082PubMedGoogle Scholar
  84. Parrella P, Xiao Y, Fliss M, Sanchez-Cespedes M, Mazzarelli P, Rinaldi M, Nicol T, Gabrielson E, Cuomo C, Cohen D, Pandit S, Spencer M, Rabitti C, Fazio VM, Sidransky D. 2001;Detection of mitochondrial DNA mutations in primary breast cancer and fine-needle aspirates. Cancer Res 61:7623–7626PubMedGoogle Scholar
  85. Pearson HA, Lobel JS, Kocoshis SA, Naiman JL, Windmiller J, Lammi AT, Hoffman R, Marsh JC. 1979;A new syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction. J Pediatr 95:976–984PubMedGoogle Scholar
  86. Penta JS, Johnson FM, Wachsman JT, Copeland WC. 2001;Mitochondrial DNA in human malignancy. Mutat Res 488:119–133PubMedGoogle Scholar
  87. Petros JA, Baumann AK, Ruiz-Pesini E, Amin MB, Sun CQ, Hall J, Lim S, Issa MM, Flanders WD, Hosseini SH, Marshall FF, Wallace DC. mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci USA 102(3):719–724. Google Scholar
  88. Polyak K, Li Y, Zhu H, Lengauer C, Willson JKV, Markowitz SD, Trush MA, Kinzler KW, Vogelstein B. 1998;Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat Genet 20:291–293PubMedGoogle Scholar
  89. Poulton J, Morten K. 1993;Noninvasive diagnosis of the MELAS syndrome from blood DNA. Ann Neurol 34:116PubMedGoogle Scholar
  90. Puigserver P, Spiegelmann BM Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coacti1 vator and metabolic regulator. 2003;24(1):78-90Google Scholar
  91. Rahman S, Poulton J, Marchington D, Suomalainen A. 2001;Decrease of 3243 A→G mtDNA mutation from blood in MELAS syndrome: a longitudinal study. Am J Hum Genet 68:238–240PubMedGoogle Scholar
  92. Rawles JM, Weller RO. 1974;Familial association of metabolic myopathy, lactic acidosis, and sideroblastic anemia. Am J Med 56:891–897PubMedGoogle Scholar
  93. Rötig A, Cormier V, Blanche S, Bonnefont J-P, Ledeist F, Romero N, Schmitz J, Rustin P, Fischer A, Saudubray J-M, Munnich A. 1990;Pearson’s marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy. J Clin Invest 86:1601–1608PubMedGoogle Scholar
  94. Rötig A, Cormier V, Koll F, Mize CE, Saudubray J-M, Veerman A, Pearson HA, Munnich A. 1991;Site-specific deletions of the mitochondrial genome in the Pearson marrow-pancreas syndrome. Genomics 10:502–504PubMedGoogle Scholar
  95. Rustin P, Rotig A. 2002;Inborn errors of complex II–unusual human mitochondrial diseases. Biochim Biophys Acta 1553:117–122.PubMedGoogle Scholar
  96. Sakamaki T, Casimiro MC, Ju X, Quong AA, Katiyar S, Liu M, Jiao X, Li A, Zhang X, Lu Y, Wang C, Byers S, Nicholson R, Link T, Shemluck M, Yang J, Fricke ST, Novikoff PM, Papanikolaou A, Arnold A, Albanese C, Pestell R. 2006;Cyclin D1 determines mitochondrial function in vivo. Mol Cell Biol 26(14):54495469Google Scholar
  97. Santoro A, Salvioli S, Raule N, Capri M, Sevini F, Valensin S, Monti D, Bellizzi D, Passarino G, Rose G, De Benedictis G, Franceschi C. 2006;Mitochondrial DNA involvement in human longevity. Biochim Biophys Acta 757(9–10):1388–1399.Google Scholar
  98. Schumacher HR, Szekely IE, Patel SB, Fisher DR. 1974;Leukemic mitochondria. I. Acute myeloblastic leukemia. Am J Pathol 74:71–82PubMedGoogle Scholar
  99. Selak MA, Armour SM, MacKenzie ED, et al. 2005;Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell 7:77–85.PubMedGoogle Scholar
  100. Shin MG, Kajigaya S, Levin BC, Young NS. 2003Mitochondrial DNA mutations in patients with myelodysplastic syndromes. Blood ;101:3118–3125PubMedGoogle Scholar
  101. Shin MG, Kajigaya S, Tarnowka M, McCoy Jr JP, Levin BC, Young NS. 2004;Mitochondrial DNA sequence heterogeneity in circulating normal human CD34 cells and granulocytes. Blood 103(12):4466–4471PubMedGoogle Scholar
  102. Shoubridge EA, Karpati G, Hastings KEM. 1990;Deletion mutants are functionally dominant over wild-type mitochondrial genomes in skeletal muscle fiber segments in mitochondrial disease. Cell 62:43–49PubMedGoogle Scholar
  103. Singh G, Lott MT, Wallace DC. 1989;A mitochondrial mutation as a cause of Leber’s hereditary optic neuropathy. N Engl J Med 36:1300–1305CrossRefGoogle Scholar
  104. Singh KK, Kulawiec M, Still I, Desouki MM, Geradts J, Matsui S. 2005;Inter-genomic cross talk between mitochondria and the nucleus plays an important role intumorigenesis. Gene 354:140–146.PubMedGoogle Scholar
  105. Singh KK 2006;Mitochondria damage checkpoint, aging, and cancer (). Ann NY Acad Sci 1067:182–190.ReviewPubMedGoogle Scholar
  106. Taylor RW, Barron MJ, Borthwick GM, Gospel A, Chinnery PF, Samuels DC, Taylor GA, Plusa SM, Needham SM, Greaves LC, Kirkwood TBL, Turnbull DM. 2003;Mitochondrial DNA mutations in human colonic crypt stem cells. J Clin Invest 112:1351–1360PubMedGoogle Scholar
  107. Tehranchi R, Fadeel B, Forsblom A-M, Christensson B, Zhivotovsky B, Hellström-Lindberg E. 2001;Evidence for a role of mitochondrial signaling in apoptosis in low-risk myelodysplastic syndromes. Blood 98:730aGoogle Scholar
  108. Verma M, Naviaux RK, Tanaka M, Kumar D, Franceschi C, Singh KK. 2007;Meeting report: mitochondrial DNA and cancer epidemiology. Cancer Res 67(2):437–439PubMedGoogle Scholar
  109. Wallace DC. 1989;Mitochondrial DNA mutations and neuromuscular disease. Trends Genet 5:9–13PubMedGoogle Scholar
  110. Wallace DC. 1992;Mitochondrial genetics: a paradigm for aging and degenerative diseases? Science 256:628–632.PubMedGoogle Scholar
  111. Wallace DC. 1999;Mitochondrial diseases in man and mouse. Science 283:1482–1488PubMedGoogle Scholar
  112. Wallace DC. 2005;A mitochondrial paradigm of Metabolic and degenerative disease, aging, and cancer. Annu Rev Genet 39:359–407PubMedGoogle Scholar
  113. Wang Y-L, Choi H-K, Heinisch J, Aul C, Gattermann N. 1999;The MERRF mutation of mitochondrial DNA in the bone marrow of a patient with acquired idiopathic sideroblastic anemia. Am J Hematol 60:83–84PubMedGoogle Scholar
  114. Warburg O. 1956;On the origin of cancer cells. Science. 123:309–314PubMedGoogle Scholar
  115. Wickramasinghe SN, Chalmers DG, Cooper EH. 1968;A study of ineffective erythropoiesis in sideroblastic anaemia and erythraemic myelosis. Cell Tissue Kinet 1:43–50Google Scholar
  116. Wickramasinghe SN, Hughes M. 1978;Capacity of ringed sideroblasts to synthesize nucleic acids and protein in patients with primary acquired sideroblastic anaemia. Br J Haematol 38:345–352PubMedGoogle Scholar
  117. Wolvetang EJ, Johnson KL, Krauer K, Ralph S, Linnane AW. 1994;Mitochondrial respiratory chain inhibitors induce apoptosis. FEBS Lett 339:40–44PubMedGoogle Scholar
  118. Yao YG, Ellison FM, McCoy JP, Chen J, Young NS. 2007;Age-dependant accumulation of mtDNA mutations in murine hematopoietic stem cells is modulated by the nuclear genetic background. Hum Mol Gen 16:286–294PubMedGoogle Scholar
  119. Zanssen S, and Buse G. 2003;Successful chemotherapy in a male patient with malignant lymphoma and Leber’s hereditary optic neuropathy (LHON). Am J Hematol 72:263–266PubMedGoogle Scholar
  120. Zanssen S, Gunawan B, Fuzesi L, et al. 2004;Renal oncocytomas with rearrangements involving 11q13 contain breakpoints near CCND1. Cancer Genet Cytogenet 149:120–124.PubMedGoogle Scholar
  121. Zanssen, and Schon (2005) Mitochondrial DNA mutations in cancer. PLOS Med 11:e401Google Scholar

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© Springer Science + Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of NeurologyCollege of Physicians & Surgeons of Columbia UniversityNew York

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