Decoding Warburg's hypothesis: Tumor-related mutations in the mitochondrial respiratory chain

Oncotarget

Volumn 6, Issue 39, 2015, Pages 41582-41599

  Garcia Heredia, Jose M ^a   Carnero, Amancio ^a  

^a UNIVERSITY OF SEVILLE   (Spain)

Author keywords

Cancer; Metabolic switch; Mitochondrial respiration; Mitochondrial respiratory chain; Warburg's hypothesis

Indexed keywords

CYTOCHROME B; CYTOCHROME C; FUMARATE HYDRATASE; MITOCHONDRIAL DNA; REACTIVE OXYGEN METABOLITE; MITOCHONDRIAL PROTEIN; MULTIENZYME COMPLEX;

ARTICLE; CANCER GROWTH; CAUSAL ATTRIBUTION; COMPLEX FORMATION; DISEASE ASSOCIATION; GENE MUTATION; HUMAN; MALIGNANT NEOPLASTIC DISEASE; MITOCHONDRIAL GENOME; MITOCHONDRIAL RESPIRATION; MTCO1 GENE; MTCO2 GENE; MTCO3 GENE; MUTATIONAL ANALYSIS; NONHUMAN; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; PHENOTYPE; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SDHA GENE; SDHAF2 GENE; SDHB GENE; SDHC GENE; SDHD GENE; TUMOR GENE; UPREGULATION; ANIMAL; CELL TRANSFORMATION; ENERGY METABOLISM; GENETIC PREDISPOSITION; GENETICS; GLYCOLYSIS; METABOLISM; MITOCHONDRION; MUTATION; NEOPLASM; PATHOLOGY; RISK FACTOR;

ANIMALS; CELL TRANSFORMATION, NEOPLASTIC; ELECTRON TRANSPORT CHAIN COMPLEX PROTEINS; ENERGY METABOLISM; GENETIC PREDISPOSITION TO DISEASE; GLYCOLYSIS; HUMANS; MITOCHONDRIA; MITOCHONDRIAL PROTEINS; MUTATION; NEOPLASMS; OXIDATIVE PHOSPHORYLATION; PHENOTYPE; RISK FACTORS;

EID: 84951823188     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.6057     Document Type: Article

References (129)

1. Warburg OP, K; Negelein, E. üeber den Stoffwechsel der Tumoren. Biochem Z. 1924; 152:319-344.
2. Warburg O. The Metabolism of Tumors. Arnold Constable, London. 1930:pp. 254-270.
3. Warburg O. On the Origin of Cancer Cells. Science. 1956; 123(3191):309-314.
4. Calabrese C, Iommarini L, Kurelac I, Calvaruso MA, Capristo M, Lollini P-L, Nanni P, Bergamini C, Nicoletti G, Giovanni CD, Ghelli A, Giorgio V, Caratozzolo MF, Marzano F, Manzari C, Betts C, et al. Respiratory complex I is essential to induce a Warburg profile in mitochondriadefective tumor cells. Cancer & Metabolism. 2013; 1(1):11.
5. Seyfried T and Shelton L. Cancer as a metabolic disease. Nutrition & Metabolism. 2010; 7(1):7.
6. Smolková K, Bellance N, Scandurra F, Génot E, Gnaiger E, Plecitá-Hlavatá L, Ježek P and Rossignol R. Mitochondrial bioenergetic adaptations of breast cancer cells to aglycemia and hypoxia. J Bioenerg Biomembr. 2010; 42(1):55-67.
7. Wise DR and Thompson CB. Glutamine addiction: a new therapeutic target in cancer. Trends in Biochemical Sciences. 35(8):427-433.
8. Marchiq I and Pouysségur J. Hypoxia, cancer metabolism and the therapeutic benefit of targeting lactate/H+ symporters. J Mol Med. 2015:1-17.
9. Kaambre T, Chekulayev V, Shevchuk I, Tepp K, Timohhina N, Varikmaa M, Bagur R, Klepinin A, Anmann T, Koit A, Kaldma A, Guzun R, Valvere V and Saks V. Metabolic control analysis of respiration in human cancer tissue. Frontiers in Physiology. 2013; 4.
10. Kaldma A, Klepinin A, Chekulayev V, Mado K, Shevchuk I, Timohhina N, Tepp K, Kandashvili M, Varikmaa M, Koit A, Planken M, Heck K, Truu L, Planken A, Valvere V, Rebane E, et al. An in situ study of bioenergetic properties of human colorectal cancer: The regulation of mitochondrial respiration and distribution of flux control among the components of ATP synthasome. The International Journal of Biochemistry & Cell Biology. 2014; 55(0):171-186.
11. Herst PM and Berridge MV. Cell surface oxygen consumption: A major contributor to cellular oxygen consumption in glycolytic cancer cell lines. Biochimica et Biophysica Acta (BBA)-Bioenergetics. 2007; 1767(2):170-177.
12. Chang C-H, Curtis Jonathan D, Maggi Leonard B, Jr., Faubert B, Villarino Alejandro V, O'Sullivan D, Huang Stanley C-C, van der Windt Gerritje JW, Blagih J, Qiu J, Weber Jason D, Pearce Edward J, Jones Russell G and Pearce Erika L. Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis. Cell. 153(6):1239-1251.
13. Colombo SL, Palacios-Callender M, Frakich N, De Leon J, Schmitt CA, Boorn L, Davis N and Moncada S. Anaphasepromoting complex/cyclosome-Cdh1 coordinates glycolysis and glutaminolysis with transition to S phase in human T lymphocytes. Proceedings of the National Academy of Sciences. 2010; 107(44):18868-18873.
14. García-Heredia JM, Felipe-Abrio B, Cano DA and Carnero A. Genetic modification of hypoxia signaling in animal models and its effect on cancer. Clin Transl Oncol. 2015; 17(2):90-102.
15. Clanton TL, Hogan MC and Gladden LB. (2013). Regulation of Cellular Gas Exchange, Oxygen Sensing, and Metabolic Control. Comprehensive Physiology: John Wiley & Sons, Inc.).
16. Loboda A, Jozkowicz A and Dulak J. HIF-1 and HIF-2 transcription factors - Similar but not identical. Mol Cells. 2010; 29(5):435-442.
17. Fandrey J, Gorr TA and Gassmann M. (2006). Regulating cellular oxygen sensing by hydroxylation.
18. Lando D, Peet DJ, Gorman JJ, Whelan DA, Whitelaw ML and Bruick RK. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes & Development. 2002; 16(12):1466-1471.
19. Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD, Pan Y, Simon MC, Thompson CB and Gottlieb E. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-a prolyl hydroxylase. Cancer Cell. 7(1):77-85.
20. Fong GH and Takeda K. Role and regulation of prolyl hydroxylase domain proteins. Cell Death Differ. 2008; 15(4):635-641.
21. Kim J-w, Tchernyshyov I, Semenza GL and Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metabolism. 2006; 3(3):177-185.
22. Papandreou I, Cairns RA, Fontana L, Lim AL and Denko NC. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metabolism. 2006; 3(3):187-197.
23. Ratcliffe PJ. Oxygen sensing and hypoxia signalling pathways in animals: the implications of physiology for cancer. The Journal of Physiology. 2013; 591(8):2027-2042.
24. Mimaki M, Wang X, McKenzie M, Thorburn DR and Ryan MT. Understanding mitochondrial complex I assembly in health and disease. Biochimica et Biophysica Acta (BBA)-Bioenergetics. 2012; 1817(6):851-862.
25. Hoekstra AS and Bayley J-P. The role of complex II in disease. Biochimica et Biophysica Acta (BBA)-Bioenergetics. 2013; 1827(5):543-551.
26. Solaini G, Sgarbi G and Baracca A. Oxidative phosphorylation in cancer cells. Biochimica et Biophysica Acta (BBA)-Bioenergetics. 2011; 1807(6):534-542.
27. Srinivasan S and Avadhani NG. Cytochrome c oxidase dysfunction in oxidative stress. Free Radical Biology and Medicine. 2012; 53(6):1252-1263.
28. Turrens JF. Mitochondrial formation of reactive oxygen species. The Journal of Physiology. 2003; 552(2):335-344.
29. Chatterjee A, Dasgupta S and Sidransky D. Mitochondrial Subversion in Cancer. Cancer Prevention Research. 2011; 4(5):638-654.
30. Musatov A and Robinson NC. Susceptibility of mitochondrial electron-transport complexes to oxidative damage. Focus on cytochrome c oxidase. Free Radical Research. 2012; 46(11):1313-1326.
31. Gasparre G, Porcelli AM, Lenaz G and Romeo G. Relevance of Mitochondrial Genetics and Metabolism in Cancer Development. Cold Spring Harbor Perspectives in Biology. 2013; 5(2).
32. Kirches E. Mitochondrial and Nuclear Genes of Mitochondrial Components in Cancer. Current Genomics. 2009; 10(4):281-293.
33. Zhou S, Kachhap S, Sun W, Wu G, Chuang A, Poeta L, Grumbine L, Mithani SK, Chatterjee A, Koch W, Westra WH, Maitra A, Glazer C, Carducci M, Sidransky D, McFate T, et al. Frequency and phenotypic implications of mitochondrial DNA mutations in human squamous cell cancers of the head and neck. Proceedings of the National Academy of Sciences. 2007; 104(18):7540-7545.
34. Tan D-J, Chang J, Chen W-L, Agress LJ, Yeh K-T, Wang B and Wong L-JC. Somatic Mitochondrial DNA Mutations in Oral Cancer of Betel Quid Chewers. Annals of the New York Academy of Sciences. 2004; 1011(1):310-316.
35. Longley MJ, Nguyen D, Kunkel TA and Copeland WC. The Fidelity of Human DNA Polymerase γ with and without Exonucleolytic Proofreading and the p55 Accessory Subunit. Journal of Biological Chemistry. 2001; 276(42):38555-38562.
36. Cadet J, Berger M, Douki T and Ravanat JL. (1997). Oxidative damage to DNA: Formation, measurement, and biological significance. Reviews of Physiology Biochemistry and Pharmacology, Volume 131: Springer Berlin Heidelberg), pp. 1-87.
37. Gasparre G, Hervouet E, de Laplanche E, Demont J, Pennisi LF, Colombel M, Mège-Lechevallier F, Scoazec J-Y, Bonora E, Smeets R, Smeitink J, Lazar V, Lespinasse J, Giraud S, Godinot C, Romeo G, et al. Clonal expansion of mutated mitochondrial DNA is associated with tumor formation and complex I deficiency in the benign renal oncocytoma. Human Molecular Genetics. 2008; 17(7):986-995.
38. Lu J, Sharma LK and Bai Y. Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis. Cell Res. 2009; 19(7):802-815.
39. Nunes JB, Peixoto J, Soares P, Maximo V, Carvalho S, Pinho SS, Vieira AF, Paredes J, Rego AC, Ferreira IL, Gomez-Lazaro M, Sobrinho-Simoes M, Singh KK and Lima J. OXPHOS dysfunction regulates integrin-β1 modifications and enhances cell motility and migration. Human Molecular Genetics. 2015; 24(7):1977-1990.
40. Brandon M, Baldi P and Wallace DC. Mitochondrial mutations in cancer. Oncogene. 2006; 25(34):4647-4662.
41. Yin P-H, Wu C-C, Lin J-C, Chi C-W, Wei Y-H and Lee H-C. Somatic mutations of mitochondrial genome in hepatocellular carcinoma. Mitochondrion. 2010; 10(2):174-182.
42. Vinothkumar KR, Zhu J and Hirst J. Architecture of mammalian respiratory complex I. Nature. 2014; 515(7525):80-84.
43. Bridges Hannah R, Birrell James A and Hirst J. (2011). The mitochondrial-encoded subunits of respiratory complex I (NADH:ubiquinone oxidoreductase): identifying residues important in mechanism and disease.
44. Hoefs SJG, van Spronsen FJ, Lenssen EWH, Nijtmans LG, Rodenburg RJ, Smeitink JAM and van den Heuvel LP. NDUFA10 mutations cause complex I deficiency in a patient with Leigh disease. Eur J Hum Genet. 2011; 19(3):270-274.
45. Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H, Nakada K, Honma Y and Hayashi J-I. ROS-Generating Mitochondrial DNA Mutations Can Regulate Tumor Cell Metastasis. Science. 2008; 320(5876):661-664.
46. Ishikawa K, Imanishi H, Takenaga K and Hayashi J-I. Regulation of metastasis; mitochondrial DNA mutations have appeared on stage. J Bioenerg Biomembr. 2012; 44(6):639-644.
47. Dmitrenko V, Shostak K, Boyko O, Khomenko O, Rozumenko V, Malisheva T, Shamayev M, Zozulya Y and Kavsan V. Reduction of the transcription level of the mitochondrial genome in human glioblastoma. Cancer Letters. 218(1):99-107.
48. Shen XY, Zacal N, Singh G and Rainbow AJ. Alterations in Mitochondrial and Apoptosis-regulating Gene Expression in Photodynamic Therapy-resistant Variants of HT29 Colon Carcinoma Cells. Photochemistry and Photobiology. 2005; 81(2):306-313.
49. Mayr JA, Meierhofer D, Zimmermann F, Feichtinger R, Kögler C, Ratschek M, Schmeller N, Sperl W and Kofler B. Loss of Complex I due to Mitochondrial DNA Mutations in Renal Oncocytoma. Clinical Cancer Research. 2008; 14(8):2270-2275.
50. Iommarini L, Calvaruso MA, Kurelac I, Gasparre G and Porcelli AM. Complex I impairment in mitochondrial diseases and cancer: Parallel roads leading to different outcomes. The International Journal of Biochemistry & Cell Biology. 2013; 45(1):47-63.
51. Tickoo SK, Lee MW, Eble JN, Amin M, Christopherson T, Zarbo RJ and Amin MB. Ultrastructural Observations on Mitochondria and Microvesicles in Renal Oncocytoma, Chromophobe Renal Cell Carcinoma, and Eosinophilic Variant of Conventional (Clear Cell) Renal Cell Carcinoma. The American Journal of Surgical Pathology. 2000; 24(9):1247-1256.
52. Gasparre G, Porcelli AM, Bonora E, Pennisi LF, Toller M, Iommarini L, Ghelli A, Moretti M, Betts CM, Martinelli GN, Ceroni AR, Curcio F, Carelli V, Rugolo M, Tallini G and Romeo G. Disruptive mitochondrial DNA mutations in complex I subunits are markers of oncocytic phenotype in thyroid tumors. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104(21):9001-9006.
53. Bonora E, Porcelli AM, Gasparre G, Biondi A, Ghelli A, Carelli V, Baracca A, Tallini G, Martinuzzi A, Lenaz G, Rugolo M and Romeo G. Defective Oxidative Phosphorylation in Thyroid Oncocytic Carcinoma Is Associated with Pathogenic Mitochondrial DNA Mutations Affecting Complexes I and III. Cancer Research. 2006; 66(12):6087-6096.
54. Hirst J. Mitochondrial Complex I. Annual Review of Biochemistry. 2013; 82(1):551-575.
55. Iommarini L, Kurelac I, Capristo M, Calvaruso MA, Giorgio V, Bergamini C, Ghelli A, Nanni P, De Giovanni C, Carelli V, Fato R, Lollini PL, Rugolo M, Gasparre G and Porcelli AM. Different mtDNA mutations modify tumor progression in dependence of the degree of respiratory complex I impairment. Human Molecular Genetics. 2014; 23(6):1453-1466.
56. Polyak K, Li Y, Zhu H, Lengauer C, Willson JKV, Markowitz SD, Trush MA, Kinzler KW and Vogelstein B. Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat Genet. 1998; 20(3):291-293.
57. Porcelli AM, Ghelli A, Ceccarelli C, Lang M, Cenacchi G, Capristo M, Pennisi LF, Morra I, Ciccarelli E, Melcarne A, Bartoletti-Stella A, SalfiN, Tallini G, Martinuzzi A, Carelli V, Attimonelli M, et al. The genetic and metabolic signature of oncocytic transformation implicates HIF1a destabilization. Human Molecular Genetics. 2010; 19(6):1019-1032.
58. Sun W, Zhou S, Chang SS, McFate T, Verma A and Califano JA. Mitochondrial Mutations Contribute to HIF1a Accumulation via Increased Reactive Oxygen Species and Up-regulated Pyruvate Dehydrogenease Kinase 2 in Head and Neck Squamous Cell Carcinoma. Clinical Cancer Research. 2009; 15(2):476-484.
59. Czarnecka A, Krawczyk T, Zdrozny M, Lubinski J, Arnold R, Kukwa W, Scinska A, Golik P, Bartnik E and Petros J. Mitochondrial NADH-dehydrogenase subunit 3 (ND3) polymorphism (A10398G) and sporadic breast cancer in Poland. Breast Cancer Res Treat. 2010; 121(2):511-518.
60. Imanishi H, Hattori K, Wada R, Ishikawa K, Fukuda S, Takenaga K, Nakada K and Hayashi J-I. Mitochondrial DNA Mutations Regulate Metastasis of Human Breast Cancer Cells. PLoS ONE. 2011; 6(8):e23401.
61. Park JS, Sharma LK, Li H, Xiang R, Holstein D, Wu J, Lechleiter J, Naylor SL, Deng JJ, Lu J and Bai Y. A heteroplasmic, not homoplasmic, mitochondrial DNA mutation promotes tumorigenesis via alteration in reactive oxygen species generation and apoptosis. Human Molecular Genetics. 2009; 18(9):1578-1589.
62. Sharma LK, Fang H, Liu J, Vartak R, Deng J and Bai Y. Mitochondrial respiratory complex I dysfunction promotes tumorigenesis through ROS alteration and AKT activation. Human Molecular Genetics. 2011; 20(23):4605-4616.
63. Yokota M, Shitara H, Hashizume O, Ishikawa K, Nakada K, Ishii R, Taya C, Takenaga K, Yonekawa H and Hayashi J-I. Generation of trans-mitochondrial mito-mice by the introduction of a pathogenic G13997A mtDNA from highly metastatic lung carcinoma cells. FEBS Letters. 2010; 584(18):3943-3948.
64. Hashizume O, Yamanashi H, Taketo MM, Nakada K and Hayashi J-I. A Specific Nuclear DNA Background Is Required for High Frequency Lymphoma Development in Transmitochondrial Mice with G13997A mtDNA. PLoS ONE. 2015; 10(3):e0118561.
65. Evangelisti C, de Biase D, Kurelac I, Ceccarelli C, Prokisch H, Meitinger T, Caria P, Vanni R, Romeo G, Tallini G, Gasparre G and Bonora E. A mutation screening of oncogenes, tumor suppressor gene TP53 and nuclear encoded mitochondrial complex I genes in oncocytic thyroid tumors. BMC Cancer. 2015; 15:157.
66. Shay JW and Werbin H. Are mitochondrial DNA mutations involved in the carcinogenic process? Mutation Research/Reviews in Genetic Toxicology. 1987; 186(2):149-160.
67. Petruzzella V and Papa S. Mutations in human nuclear genes encoding for subunits of mitochondrial respiratory complex I: the NDUFS4 gene. Gene. 2002; 286(1):149-154.
68. Pitkanen S and Robinson BH. Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase. The Journal of Clinical Investigation. 1996; 98(2):345-351.
69. Bardella C, Pollard PJ and Tomlinson I. SDH mutations in cancer. Biochimica et Biophysica Acta (BBA)-Bioenergetics. 2011; 1807(11):1432-1443.
70. Pantaleo MA, AstolfiA, Urbini M, Nannini M, Paterini P, Indio V, Saponara M, Formica S, Ceccarelli C, Casadio R, Rossi G, Bertolini F, Santini D, Pirini MG, Fiorentino M, Basso U, et al. Analysis of all subunits, SDHA, SDHB, SDHC, SDHD, of the succinate dehydrogenase complex in KIT/PDGFRA wild-type GIST. Eur J Hum Genet. 2014; 22(1):32-39.
71. Hao H-X, Khalimonchuk O, Schraders M, Dephoure N, Bayley J-P, Kunst H, Devilee P, Cremers CWRJ, Schiffman JD, Bentz BG, Gygi SP, Winge DR, Kremer H and Rutter J. SDH5, a Gene Required for Flavination of Succinate Dehydrogenase, Is Mutated in Paraganglioma. Science (New York, NY). 2009; 325(5944):10.1126/science.1175689.
72. Wagner AJ, Remillard SP, Zhang Y-X, Doyle LA, George S and Hornick JL. Loss of expression of SDHA predicts SDHA mutations in gastrointestinal stromal tumors. Mod Pathol. 2013; 26(2):289-294.
73. Korpershoek E, Favier J, Gaal J, Burnichon N, Gessel Bv, Oudijk L, Badoual C, Gadessaud N, Venisse A, Bayley J-P, Dooren MFv, Herder WWd, Tissier F, Plouin P-F, Nederveen FHv, Dinjens WNM, et al. SDHA Immunohistochemistry Detects Germline SDHA Gene Mutations in Apparently Sporadic Paragangliomas and Pheochromocytomas. The Journal of Clinical Endocrinology & Metabolism. 2011; 96(9):E1472-E1476.
74. Ricketts C, Woodward ER, Killick P, Morris MR, Astuti D, Latif F and Maher ER. Germline SDHB Mutations and Familial Renal Cell Carcinoma. Journal of the National Cancer Institute. 2008; 100(17):1260-1262.
75. Douwes Dekker PB, Hogendoorn PCW, Kuipers-Dijkshoorn N, Prins FA, van Duinen SG, Taschner PEM, van der Mey AGL and Cornelisse CJ. SDHD mutations in head and neck paragangliomas result in destabilization of complex II in the mitochondrial respiratory chain with loss of enzymatic activity and abnormal mitochondrial morphology. The Journal of Pathology. 2003; 201(3):480-486.
76. Mannelli M, Ercolino T, Giachè V, Simi L, Cirami C and Parenti G. Genetic screening for pheochromocytoma: should SDHC gene analysis be included? Journal of Medical Genetics. 2007; 44(9):586-587.
77. Peczkowska M, Cascon A, Prejbisz A, Kubaszek A, B Cwikla J, Furmanek M, Erlic Z, Eng C, Januszewicz A and Neumann HPH. Extra-adrenal and adrenal pheochromocytomas associated with a germline SDHC mutation. Nat Clin Pract End Met. 2008; 4(2):111-115.
78. Ishii N, Ishii T and Hartman PS. The role of the electron transport SDHC gene on lifespan and cancer. Mitochondrion. 2007; 7(1-2):24-28.
79. Erlic Z, Rybicki L, Peczkowska M, Golcher H, Kann PH, BrauckhoffM, Müssig K, Muresan M, Schäffler A, Reisch N, Schott M, Fassnacht M, Opocher G, Klose S, Fottner C, Forrer F, et al. Clinical Predictors and Algorithm for the Genetic Diagnosis of Pheochromocytoma Patients. Clinical Cancer Research. 2009; 15(20):6378-6385.
80. Bayley J-P and Devilee P. Warburg tumours and the mechanisms of mitochondrial tumour suppressor genes. Barking up the right tree? Current Opinion in Genetics & Development. 2010; 20(3):324-329.
81. Bayley J-P, Kunst HPM, Cascon A, Sampietro ML, Gaal J, Korpershoek E, Hinojar-Gutierrez A, Timmers HJLM, Hoefsloot LH, Hermsen MA, Suárez C, Hussain AK, Vriends AHJT, Hes FJ, Jansen JC, Tops CM, et al. SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma. The Lancet Oncology. 2010; 11(4):366-372.
82. Alam N, Barclay E, Rowan AJ and et al. Clinical features of multiple cutaneous and uterine leiomyomatosis: An underdiagnosed tumor syndrome. Archives of Dermatology. 2005; 141(2):199-206.
83. Brière J-J, Favier J, Bénit P, Ghouzzi VE, Lorenzato A, Rabier D, Di Renzo MF, Gimenez-Roqueplo A-P and Rustin P. Mitochondrial succinate is instrumental for HIF1a nuclear translocation in SDHA-mutant fibroblasts under normoxic conditions. Human Molecular Genetics. 2005; 14(21):3263-3269.
84. Pollard PJ, Brière JJ, Alam NA, Barwell J, Barclay E, Wortham NC, Hunt T, Mitchell M, Olpin S, Moat SJ, Hargreaves IP, Heales SJ, Chung YL, Griffiths JR, Dalgleish A, McGrath JA, et al. Accumulation of Krebs cycle intermediates and over-expression of HIF1a in tumours which result from germline FH and SDH mutations. Human Molecular Genetics. 2005; 14(15):2231-2239.
85. Kim S, Kim D, Jung W-H and Koo J. Succinate dehydrogenase expression in breast cancer. SpringerPlus. 2013; 2(1):299.
86. Bayley J-P, van Minderhout I, Hogendoorn PCW, Cornelisse CJ, van der Wal A, Prins FA, Teppema L, Dahan A, Devilee P and Taschner PEM. Sdhd and Sdhd/H19 Knockout Mice Do Not Develop Paraganglioma or Pheochromocytoma. PLoS ONE. 2009; 4(11):e7987.
87. Piruat JI, Pintado CO, Ortega-Sáenz P, Roche M and López-Barneo J. The Mitochondrial SDHD Gene Is Required for Early Embryogenesis, and Its Partial Deficiency Results in Persistent Carotid Body Glomus Cell Activation with Full Responsiveness to Hypoxia. Molecular and Cellular Biology. 2004; 24(24):10933-10940.
88. Bénit P, Lebon S and Rustin P. Respiratory-chain diseases related to complex III deficiency. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2009; 1793(1):181-185.
89. Valnot I, Kassis J, Chretien D, de Lonlay P, Parfait B, Munnich A, Kachaner J, Rustin P and Rötig A. A mitochondrial cytochrome b mutation but no mutations of nuclearly encoded subunits in ubiquinol cytochrome c reductase (complex III) deficiency. Hum Genet. 1999; 104(6):460-466.
90. Bell EL, Klimova TA, Eisenbart J, Moraes CT, Murphy MP, Budinger GRS and Chandel NS. The Q(o) site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production. The Journal of Cell Biology. 2007; 177(6):1029-1036.
91. Dasgupta S, Hoque MO, Upadhyay S and Sidransky D. Mitochondrial Cytochrome B Gene Mutation Promotes Tumor Growth in Bladder Cancer. Cancer Research. 2008; 68(3):700-706.
92. Ott M, Robertson JD, Gogvadze V, Zhivotovsky B and Orrenius S. Cytochrome c release from mitochondria proceeds by a two-step process. Proceedings of the National Academy of Sciences. 2002; 99(3):1259-1263.
93. Hüttemann M, Pecina P, Rainbolt M, Sanderson TH, Kagan VE, Samavati L, Doan JW and Lee I. The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: From respiration to apoptosis. Mitochondrion. 2011; 11(3):369-381.
94. Jiang X and Wang X. CYTOCHROME C-MEDIATED APOPTOSIS. Annual Review of Biochemistry. 2004; 73(1):87-106.
95. Kulikov AV, Shilov ES, Mufazalov IA, Gogvadze V, Nedospasov SA and Zhivotovsky B. Cytochrome c: the Achilles' heel in apoptosis. Cell Mol Life Sci. 2012; 69(11):1787-1797.
96. Yoo NJ, Soung YH and Lee SH. Absence of pro-apoptotic cytochrome c gene mutation in common solid cancers and acute leukaemias. Pathology-Journal of the RCPA. 2009; 41(4):395-396.
97. De Rocco D, Cerqua C, Goffrini P, Russo G, Pastore A, Meloni F, Nicchia E, Moraes CT, Pecci A, Salviati L and Savoia A. Mutations of cytochrome c identified in patients with thrombocytopenia THC4 affect both apoptosis and cellular bioenergetics. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2014; 1842(2):269-274.
98. Hüttemann M, Helling S, Sanderson TH, Sinkler C, Samavati L, Mahapatra G, Varughese A, Lu G, Liu J, Ramzan R, Vogt S, Grossman LI, Doan JW, Marcus K and Lee I. Regulation of mitochondrial respiration and apoptosis through cell signaling: Cytochrome c oxidase and cytochrome c in ischemia/reperfusion injury and inflammation. Biochimica et Biophysica Acta (BBA)-Bioenergetics. 2012; 1817(4):598-609.
99. Pecina P, Borisenko GG, Belikova NA, Tyurina YY, Pecinova A, Lee I, Samhan-Arias AK, Przyklenk K, Kagan VE and Hüttemann M. Phosphomimetic Substitution of Cytochrome c Tyrosine 48 Decreases Respiration and Binding to Cardiolipin and Abolishes Ability to Trigger Downstream Caspase Activation. Biochemistry. 2010; 49(31):6705-6714.
100. Belevich I, Verkhovsky MI and Wikström M. Protoncoupled electron transfer drives the proton pump of cytochrome c oxidase. Nature. 2006; 440(7085):829-832.
101. Capaldi RA. Structure and Function of Cytochrome c Oxidase. Annual Review of Biochemistry. 1990; 59(1):569-596.
102. Petros JA, Baumann AK, Ruiz-Pesini E, Amin MB, Sun CQ, Hall J, Lim S, Issa MM, Flanders WD, Hosseini SH, Marshall FF and Wallace DC. mtDNA mutations increase tumorigenicity in prostate cancer. Proceedings of the National Academy of Sciences of the United States of America. 2005; 102(3):719-724.
103. Gallardo ME, Moreno-Loshuertos R, López C, Casqueiro M, Silva J, Bonilla F, de Córdoba SR and Enríquez JA. m.6267G>A: a recurrent mutation in the human mitochondrial DNA that reduces cytochrome c oxidase activity and is associated with tumors. Human Mutation. 2006; 27(6):575-582.
104. Arnold RS, Sun Q, Sun CQ, Richards JC, O'Hearn S, Osunkoya AO, Wallace DC and Petros JA. An Inherited Heteroplasmic Mutation in Mitochondrial Gene COI in a Patient with Prostate Cancer Alters Reactive Oxygen, Reactive Nitrogen and Proliferation. BioMed Research International. 2013; 2013:10.
105. Namslauer I and Brzezinski P. A mitochondrial DNA mutation linked to colon cancer results in proton leaks in cytochrome c oxidase. Proceedings of the National Academy of Sciences. 2009; 106(9):3402-3407.
106. Silkjaer T, Nyvold CG, Juhl-Christensen C, Hokland P and Nørgaard JM. Mitochondrial cytochrome c oxidase subunit II variations predict adverse prognosis in cytogenetically normal acute myeloid leukaemia. European Journal of Haematology. 2013; 91(4):295-303.
107. Prabu SK, Anandatheerthavarada HK, Raza H, Srinivasan S, Spear JF and Avadhani NG. Protein Kinase A-mediated Phosphorylation Modulates Cytochrome c Oxidase Function and Augments Hypoxia and Myocardial Ischemiarelated Injury. Journal of Biological Chemistry. 2006; 281(4):2061-2070.
108. Jonckheere AI, Smeitink JAM and Rodenburg RJT. Mitochondrial ATP synthase: architecture, function and pathology. J Inherit Metab Dis. 2012; 35(2):211-225.
109. Ghaffarpour M, Mahdian R, Fereidooni F, Kamalidehghan B, Moazami N and Houshmand M. The mitochondrial ATPase6 gene is more susceptible to mutation than the ATPase8 gene in breast cancer patients. Cancer Cell International. 2014; 14(1):21.
110. Shidara Y, Yamagata K, Kanamori T, Nakano K, Kwong JQ, Manfredi G, Oda H and Ohta S. Positive Contribution of Pathogenic Mutations in the Mitochondrial Genome to the Promotion of Cancer by Prevention from Apoptosis. Cancer Research. 2005; 65(5):1655-1663.
111. Shiraiwa N, Ishii A, Iwamoto H, Mizusawa H, Kagawa Y and Ohta S. Content of mutant mitochondrial DNA and organ dysfunction in a patient with a MELAS subgroup of mitochondrial encephalomyopathies. Journal of the Neurological Sciences. 1993; 120(2):174-179.
112. García JJ, Ogilvie I, Robinson BH and Capaldi RA. Structure, Functioning, and Assembly of the ATP Synthase in Cells from Patients with the T8993G Mitochondrial DNA Mutation: COMPARISON WITH THE ENZYME IN Rho0 CELLS COMPLETELY LACKING mtDNA. Journal of Biological Chemistry. 2000; 275(15):11075-11081.
113. Arnold RS, Sun CQ, Richards JC, Grigoriev G, Coleman IM, Nelson PS, Hsieh C-L, Lee JK, Xu Z, Rogatko A, Osunkoya AO, Zayzafoon M, Chung L and Petros JA. Mitochondrial DNA Mutation Stimulates Prostate Cancer Growth in Bone Stromal Environment. The Prostate. 2009; 69(1):1-11.
114. Wang C-Y, Wang H-W, Yao Y-G, Kong Q-P and Zhang Y-P. Somatic mutations of mitochondrial genome in early stage breast cancer. International Journal of Cancer. 2007; 121(6):1253-1256.
115. Fulda S, Galluzzi L and Kroemer G. Targeting mitochondria for cancer therapy. Nat Rev Drug Discov. 2010; 9(6):447-464.
116. Guerra F, Perrone AM, Kurelac I, Santini D, Ceccarelli C, Cricca M, Zamagni C, De Iaco P and Gasparre G. Mitochondrial DNA Mutation in Serous Ovarian Cancer: Implications for Mitochondria-Coded Genes in Chemoresistance. Journal of Clinical Oncology. 2012; 30(36):e373-e378.
117. Carew JS, Zhou Y, Albitar M, Carew JD, Keating MJ and Huang P. Mitochondrial DNA mutations in primary leukemia cells after chemotherapy: clinical significance and therapeutic implications. Leukemia. 2003; 17(8):1437-1447.
118. Lebrecht D, Setzer B, Ketelsen U-P, Haberstroh J and Walker UA. Time-Dependent and Tissue-Specific Accumulation of mtDNA and Respiratory Chain Defects in Chronic Doxorubicin Cardiomyopathy. Circulation. 2003; 108(19):2423-2429.
119. Peng X and Gandhi V. ROS-activated anticancer prodrugs: a new strategy for tumor-specific damage. Therapeutic delivery. 2012; 3(7):823-833.
120. Ishii T, Yasuda K, Akatsuka A, Hino O, Hartman PS and Ishii N. A Mutation in the SDHC Gene of Complex II Increases Oxidative Stress, Resulting in Apoptosis and Tumorigenesis. Cancer Research. 2005; 65(1):203-209.
121. Ishii T, Miyazawa M, Onodera A, Yasuda K, Kawabe N, Kirinashizawa M, Yoshimura S, Maruyama N, Hartman PS and Ishii N. Mitochondrial reactive oxygen species generation by the SDHC V69E mutation causes low birth weight and neonatal growth retardation. Mitochondrion. 2011; 11(1):155-165.
122. Quinlan CL, Orr AL, Perevoshchikova IV, Treberg JR, Ackrell BA and Brand MD. Mitochondrial Complex II Can Generate Reactive Oxygen Species at High Rates in Both the Forward and Reverse Reactions. Journal of Biological Chemistry. 2012; 287(32):27255-27264.
123. Kluckova K, Bezawork-Geleta A, Rohlena J, Dong L and Neuzil J. Mitochondrial complex II, a novel target for anticancer agents. Biochimica et Biophysica Acta (BBA)-Bioenergetics. 2013; 1827(5):552-564.
124. Pistollato F, Abbadi S, Rampazzo E, Viola G, Puppa AD, Cavallini L, Frasson C, Persano L, Panchision DM and Basso G. Hypoxia and succinate antagonize 2-deoxyglucose effects on glioblastoma. Biochemical Pharmacology. 2010; 80(10):1517-1527.
125. Zhang D, Li J, Wang F, Hu J, Wang S and Sun Y. 2-Deoxy-D-glucose targeting of glucose metabolism in cancer cells as a potential therapy. Cancer Letters. 2014; 355(2):176-183.
126. Storozhuk Y, Hopmans SN, Sanli T, Barron C, Tsiani E, Cutz JC, Pond G, Wright J, Singh G and Tsakiridis T. Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK. Br J Cancer. 2013; 108(10):2021-2032.
127. Song CW, Lee H, Dings RPM, Williams B, Powers J, Santos TD, Choi B-H and Park HJ. Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells. Scientific Reports. 2012; 2:362.
128. Putignani L, Raffa S, Pescosolido R, Aimati L, Signore F, Torrisi M and Grammatico P. Alteration of expression levels of the oxidative phosphorylation system (OXPHOS) in breast cancer cell mitochondria. Breast Cancer Res Treat. 2008; 110(3):439-452.
129. Mizutani S, Miyato Y, Shidara Y, Asoh S, Tokunaga A, Tajiri T and Ohta S. Mutations in the mitochondrial genome confer resistance of cancer cells to anticancer drugs. Cancer Science. 2009; 100(9):1680-1687.