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Mitochondrial Mutations in Cancer Progression: Causative, Bystanders, or Modifiers of Tumorigenesis?

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Tumor Cell Metabolism

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Abstract

Mitochondrial DNA encodes genes that are de facto metabolic enzymes and are currently emerging as pivotal players in the origin, progression, and outcome of human cancers. We here revise the multifaceted implications of mitochondrial mutations on the metabolic reprogramming cancer cells must undergo to adapt and proliferate. The sources of such mutations and the processes that govern their positive selection are described, along with the consequences that a deranged respiratory metabolism may have on the remodeling that follows oncogenes activation or tumor suppressors ablation. Ultimately, we dwell on the peculiar features of oncocytic tumors, one of the most relevant yet mysterious models to functionally investigate the role of mitochondrial mutations in cancer.

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References

  • Aanen DK, Maas MF (2012) Recruitment of healthy mitochondria fuels transmissible cancers. Trends Genet 28:1–6

    CAS  PubMed  Google Scholar 

  • Akhtar M, Kott E (1979) Oncocytoma of kidney. Urology 14:397–400

    CAS  PubMed  Google Scholar 

  • Alderson NL, Wang Y, Blatnik M, Frizzell N, Walla MD, Lyons TJ et al (2006) S-(2-Succinyl)cysteine: a novel chemical modification of tissue proteins by a Krebs cycle intermediate. Arch Biochem Biophys 450:1–8

    CAS  PubMed  Google Scholar 

  • Alexeyev M, Shokolenko I, Wilson G, LeDoux S (2013) The maintenance of mitochondrial DNA integrity—critical analysis and update. Cold Spring Harb Perspect Biol 5:a012641

    PubMed Central  PubMed  Google Scholar 

  • Alsbeih GA, Al-Harbi NM, El-Sebaie MM, Al-Rajhi NM, Al-Hadyan KS, Abu-Amero KK (2009) Involvement of mitochondrial DNA sequence variations and respiratory activity in late complications following radiotherapy. Clin Cancer Res 15:7352–7360

    CAS  PubMed  Google Scholar 

  • Amati-Bonneau P, Valentino ML, Reynier P, Gallardo ME, Bornstein B, Boissiere A et al (2008) OPA1 mutations induce mitochondrial DNA instability and optic atrophy ‘plus’ phenotypes. Brain 131:338–351

    PubMed  Google Scholar 

  • Amuthan G, Biswas G, Ananadatheerthavarada HK, Vijayasarathy C, Shephard HM, Avadhani NG (2002) Mitochondrial stress-induced calcium signaling, phenotypic changes and invasive behavior in human lung carcinoma A549 cells. Oncogene 21:7839–7849

    CAS  PubMed  Google Scholar 

  • Arnold RS, Sun Q, Sun CQ, Richards JC, O’Hearn S, Osunkoya AO et al (2013) An inherited heteroplasmic mutation in mitochondrial gene COI in a patient with prostate cancer alters reactive oxygen, reactive nitrogen and proliferation. Biomed Res Int 2013:239257

    PubMed Central  PubMed  Google Scholar 

  • Arnould T, Vankoningsloo S, Renard P, Houbion A, Ninane N, Demazy C et al (2002) CREB activation induced by mitochondrial dysfunction is a new signaling pathway that impairs cell proliferation. EMBO J 21:53–63

    PubMed Central  CAS  PubMed  Google Scholar 

  • Astuti D, Douglas F, Lennard TW, Aligianis IA, Woodward ER, Evans DG et al (2001) Germline SDHD mutation in familial phaeochromocytoma. Lancet 357:1181–1182

    CAS  PubMed  Google Scholar 

  • Baradaran R, Berrisford JM, Minhas GS, Sazanov LA (2013) Crystal structure of the entire respiratory complex I. Nature 494:443–448

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bartoletti-Stella A, Mariani E, Kurelac I, Maresca A, Caratozzolo MF, Iommarini L et al (2013) Gamma rays induce a p53-independent mitochondrial biogenesis that is counter-regulated by HIF1alpha. Cell Death Dis 4:e663

    PubMed Central  CAS  PubMed  Google Scholar 

  • Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A et al (2000) Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287:848–851

    CAS  PubMed  Google Scholar 

  • Bellizzi D, D’Aquila P, Giordano M, Montesanto A, Passarino G (2012) Global DNA methylation levels are modulated by mitochondrial DNA variants. Epigenomics 4:17–27

    CAS  PubMed  Google Scholar 

  • Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R et al (2006) TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 126:107–120

    CAS  PubMed  Google Scholar 

  • Biswas G, Adebanjo OA, Freedman BD, Anandatheerthavarada HK, Vijayasarathy C, Zaidi M et al (1999) Retrograde Ca2+ signaling in C2C12 skeletal myocytes in response to mitochondrial genetic and metabolic stress: a novel mode of inter-organelle crosstalk. EMBO J 18:522–533

    PubMed Central  CAS  PubMed  Google Scholar 

  • Boesch P, Weber-Lotfi F, Ibrahim N, Tarasenko V, Cosset A, Paulus F et al (2010) DNA repair in organelles: pathways, organization, regulation, relevance in disease and aging. Biochim Biophys Acta 1813:186–200

    PubMed  Google Scholar 

  • Bonnet C, Kaltimbacher V, Ellouze S, Augustin S, Benit P, Forster V et al (2007) Allotopic mRNA localization to the mitochondrial surface rescues respiratory chain defects in fibroblasts harboring mitochondrial DNA mutations affecting complex I or v subunits. Rejuvenation Res 10:127–144

    CAS  PubMed  Google Scholar 

  • Brandon M, Baldi P, Wallace DC (2006) Mitochondrial mutations in cancer. Oncogene 25:4647–4662

    CAS  PubMed  Google Scholar 

  • Bungard D, Fuerth BJ, Zeng PY, Faubert B, Maas NL, Viollet B et al (2010) Signaling kinase AMPK activates stress-promoted transcription via histone H2B phosphorylation. Science 329:1201–1205

    PubMed Central  CAS  PubMed  Google Scholar 

  • Burney S, Caulfield JL, Niles JC, Wishnok JS, Tannenbaum SR (1999) The chemistry of DNA damage from nitric oxide and peroxynitrite. Mutat Res 424:37–49

    CAS  PubMed  Google Scholar 

  • Cairns RA, Harris IS, Mak TW (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11:85–95

    CAS  PubMed  Google Scholar 

  • Calabrese C, Iommarini L, Kurelac I, Calvaruso MA, Capristo M, Lollini PL et al (2013) Respiratory complex I is essential to induce a Warburg profile in mitochondria-defective tumor cells. Cancer Metab 1:11

    PubMed Central  PubMed  Google Scholar 

  • Calabrese C, Simone D, Diroma MA, Santorsola M, Guttà C, Gasparre G, Picardi E, Pesole G, Attimonelli M (2014) MToolBox: a highly automated pipeline for heteroplasmy annotation and prioritization analysis of human mitochondrial variants in high-throughput sequencing. Bioinformatics pii:btu483

    Google Scholar 

  • Campbell CT, Kolesar JE, Kaufman BA (2012) Mitochondrial transcription factor A regulates mitochondrial transcription initiation, DNA packaging, and genome copy number. Biochim Biophys Acta 1819:921–929

    CAS  PubMed  Google Scholar 

  • Canter JA, Kallianpur AR, Parl FF, Millikan RC (2005) Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Res 65:8028–8033

    CAS  PubMed  Google Scholar 

  • Carelli V, Baracca A, Barogi S, Pallotti F, Valentino ML, Montagna P et al (2002) Biochemical-clinical correlation in patients with different loads of the mitochondrial DNA T8993G mutation. Arch Neurol 59:264–270

    PubMed  Google Scholar 

  • Carew JS, Zhou Y, Albitar M, Carew JD, Keating MJ, Huang P (2003) Mitochondrial DNA mutations in primary leukemia cells after chemotherapy: clinical significance and therapeutic implications. Leukemia 17:1437–1447

    CAS  PubMed  Google Scholar 

  • Cavalli LR, Varella-Garcia M, Liang BC (1997) Diminished tumorigenic phenotype after depletion of mitochondrial DNA. Cell Growth Differ 8:1189–1198

    CAS  PubMed  Google Scholar 

  • Cervera AM, Bayley JP, Devilee P, McCreath KJ (2009) Inhibition of succinate dehydrogenase dysregulates histone modification in mammalian cells. Mol Cancer 8:89

    PubMed Central  PubMed  Google Scholar 

  • Chandel NS, McClintock DS, Feliciano CE, Wood TM, Melendez JA, Rodriguez AM et al (2000) Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J Biol Chem 275:25130–25138

    CAS  PubMed  Google Scholar 

  • Chatterjee A, Dasgupta S, Sidransky D (2011) Mitochondrial subversion in cancer. Cancer Prev Res (Phila) 4:638–654

    CAS  Google Scholar 

  • Chatterjee A, Mambo E, Sidransky D (2006) Mitochondrial DNA mutations in human cancer. Oncogene 25:4663–4674

    CAS  PubMed  Google Scholar 

  • Chen PL, Chen CF, Chen Y, Guo XE, Huang CK, Shew JY et al (2012) Mitochondrial genome instability resulting from SUV3 haploinsufficiency leads to tumorigenesis and shortened lifespan. Oncogene 32:1193–1201

    PubMed Central  PubMed  Google Scholar 

  • Chiarugi A, Dolle C, Felici R, Ziegler M (2012) The NAD metabolome—a key determinant of cancer cell biology. Nat Rev Cancer 12:741–752

    CAS  PubMed  Google Scholar 

  • Chiche J, Brahimi-Horn MC, Pouyssegur J (2010) Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer. J Cell Mol Med 14:771–794

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chinnery PF, Elliott HR, Hudson G, Samuels DC, Relton CL (2012) Epigenetics, epidemiology and mitochondrial DNA diseases. Int J Epidemiol 41:177–187

    PubMed Central  PubMed  Google Scholar 

  • Cline SD (2012) Mitochondrial DNA damage and its consequences for mitochondrial gene expression. Biochim Biophys Acta 1819:979–991

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cloos CR, Daniels DH, Kalen A, Matthews K, Du J, Goswami PC et al (2009) Mitochondrial DNA depletion induces radioresistance by suppressing G2 checkpoint activation in human pancreatic cancer cells. Radiat Res 171:581–587

    PubMed Central  CAS  PubMed  Google Scholar 

  • 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 28:147–150

    CAS  PubMed  Google Scholar 

  • Cook CC, Higuchi M (2012) The awakening of an advanced malignant cancer: an insult to the mitochondrial genome. Biochim Biophys Acta 1820:652–662

    PubMed Central  CAS  PubMed  Google Scholar 

  • Copeland WC, Ponamarev MV, Nguyen D, Kunkel TA, Longley MJ (2003) Mutations in DNA polymerase gamma cause error prone DNA synthesis in human mitochondrial disorders. Acta Biochim Pol 50:155–167

    CAS  PubMed  Google Scholar 

  • Cuezva JM, Ortega AD, Willers I, Sanchez-Cenizo L, Aldea M, Sanchez-Arago M (2009) The tumor suppressor function of mitochondria: translation into the clinics. Biochim Biophys Acta 1792:1145–1158

    CAS  PubMed  Google Scholar 

  • Damiani S, Eusebi V, Losi L, D’Adda T, Rosai J (1998) Oncocytic carcinoma (malignant oncocytoma) of the breast. Am J Surg Pathol 22:221–230

    CAS  PubMed  Google Scholar 

  • Dasgupta S, Hoque MO, Upadhyay S, Sidransky D (2008) Mitochondrial cytochrome B gene mutation promotes tumor growth in bladder cancer. Cancer Res 68:700–706

    CAS  PubMed  Google Scholar 

  • DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7:11–20

    CAS  PubMed  Google Scholar 

  • DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S et al (2007) Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA 104:19345–19350

    PubMed Central  CAS  PubMed  Google Scholar 

  • Denver DR, Morris K, Lynch M, Vassilieva LL, Thomas WK (2000) High direct estimate of the mutation rate in the mitochondrial genome of Caenorhabditis elegans. Science 289:2342–2344

    CAS  PubMed  Google Scholar 

  • Desler C, Munch-Petersen B, Stevnsner T, Matsui S, Kulawiec M, Singh KK et al (2007) Mitochondria as determinant of nucleotide pools and chromosomal stability. Mutat Res 625:112–124

    CAS  PubMed  Google Scholar 

  • Elachouri G, Vidoni S, Zanna C, Pattyn A, Boukhaddaoui H, Gaget K et al (2011) OPA1 links human mitochondrial genome maintenance to mtDNA replication and distribution. Genome Res 21:12–20

    PubMed Central  CAS  PubMed  Google Scholar 

  • Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR et al (2004) Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 64:3892–3899

    CAS  PubMed  Google Scholar 

  • Faubert B, Boily G, Izreig S, Griss T, Samborska B, Dong Z et al (2013) AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo. Cell Metab 17:113–124

    PubMed Central  CAS  PubMed  Google Scholar 

  • Feron O (2009) Pyruvate into lactate and back: from the Warburg effect to symbiotic energy fuel exchange in cancer cells. Radiother Oncol 92:329–333

    CAS  PubMed  Google Scholar 

  • Freyer C, Cree LM, Mourier A, Stewart JB, Koolmeister C, Milenkovic D et al (2012) Variation in germline mtDNA heteroplasmy is determined prenatally but modified during subsequent transmission. Nat Genet 44:1282–1285

    PubMed Central  CAS  PubMed  Google Scholar 

  • Galluzzi L, Morselli E, Kepp O, Vitale I, Rigoni A, Vacchelli E et al (2010) Mitochondrial gateways to cancer. Mol Aspects Med 31:1–20

    CAS  PubMed  Google Scholar 

  • Gasparre G, Bonora E, Tallini G, Romeo G (2010a) Molecular features of thyroid oncocytic tumors. Mol Cell Endocrinol 321:67–76

    CAS  PubMed  Google Scholar 

  • Gasparre G, Hervouet E, de Laplanche E, Demont J, Pennisi LF, Colombel M et al (2008) Clonal expansion of mutated mitochondrial DNA is associated with tumor formation and complex I deficiency in the benign renal oncocytoma. Hum Mol Genet 17:986–995

    CAS  PubMed  Google Scholar 

  • Gasparre G, Iommarini L, Porcelli AM, Lang M, Ferri GG, Kurelac I et al (2009) An inherited mitochondrial DNA disruptive mutation shifts to homoplasmy in oncocytic tumor cells. Hum Mutat 30:391–396

    CAS  PubMed  Google Scholar 

  • Gasparre G, Kurelac I, Capristo M, Iommarini L, Ghelli A, Ceccarelli C et al (2011) A mutation threshold distinguishes the antitumorigenic effects of the mitochondrial gene MTND1, an oncojanus function. Cancer Res 71:6220–6229

    CAS  PubMed  Google Scholar 

  • Gasparre G, Porcelli AM, Bonora E, Pennisi LF, Toller M, Iommarini L et al (2007) Disruptive mitochondrial DNA mutations in complex I subunits are markers of oncocytic phenotype in thyroid tumors. Proc Natl Acad Sci USA 104:9001–9006

    PubMed Central  CAS  PubMed  Google Scholar 

  • Gasparre G, Romeo G, Rugolo M, Porcelli AM (2010b) Learning from oncocytic tumors: why choose inefficient mitochondria? Biochim Biophys Acta 1807:633–642

    PubMed  Google Scholar 

  • Gochhait S, Bhatt A, Sharma S, Singh YP, Gupta P, Bamezai RN (2008) Concomitant presence of mutations in mitochondrial genome and p53 in cancer development—a study in north Indian sporadic breast and esophageal cancer patients. Int J Cancer 123:2580–2586

    CAS  PubMed  Google Scholar 

  • Gozuacik D, Kimchi A (2004) Autophagy as a cell death and tumor suppressor mechanism. Oncogene 23:2891–2906

    CAS  PubMed  Google Scholar 

  • Green DR, Kroemer G (2009) Cytoplasmic functions of the tumour suppressor p53. Nature 458:1127–1130

    PubMed Central  CAS  PubMed  Google Scholar 

  • Green DR, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305:626–629

    CAS  PubMed  Google Scholar 

  • Guerra F, Kurelac I, Cormio A, Zuntini R, Amato LB, Ceccarelli C et al (2011) Placing mitochondrial DNA mutations within the progression model of type I endometrial carcinoma. Hum Mol Genet 20:2394–2405

    CAS  PubMed  Google Scholar 

  • Guerra F, Perrone AM, Kurelac I, Santini D, Ceccarelli C, Cricca M et al (2012) Mitochondrial DNA mutation in serous ovarian cancer: implications for mitochondria-coded genes in chemoresistance. J Clin Oncol 30:e373–e378

    PubMed  Google Scholar 

  • Guha M, Avadhani NG (2013) Mitochondrial retrograde signaling at the crossroads of tumor bioenergetics, genetics and epigenetics. Mitochondrion 13:577–591

    CAS  PubMed  Google Scholar 

  • Guo JY, Chen HY, Mathew R, Fan J, Strohecker AM, Karsli-Uzunbas G et al (2011) Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev 25:460–470

    PubMed Central  CAS  PubMed  Google Scholar 

  • Guo JY, Karsli-Uzunbas G, Mathew R, Aisner SC, Kamphorst JJ, Strohecker AM et al (2013) Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes Dev 27:1447–1461

    PubMed Central  CAS  PubMed  Google Scholar 

  • Guzy RD, Hoyos B, Robin E, Chen H, Liu L, Mansfield KD et al (2005) Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab 1:401–408

    CAS  PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    CAS  PubMed  Google Scholar 

  • Hardie DG (2011) AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev 25:1895–1908

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hasmann M, Schemainda I (2003) FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis. Cancer Res 63:7436–7442

    CAS  PubMed  Google Scholar 

  • Hazkani-Covo E, Zeller RM, Martin W (2010) Molecular poltergeists: mitochondrial DNA copies (numts) in sequenced nuclear genomes. PLoS Genet 6:e1000834

    PubMed Central  PubMed  Google Scholar 

  • He Y, Wu J, Dressman DC, Iacobuzio-Donahue C, Markowitz SD, Velculescu VE et al (2010) Heteroplasmic mitochondrial DNA mutations in normal and tumour cells. Nature 464:610–614

    PubMed Central  CAS  PubMed  Google Scholar 

  • Higuchi M, Manna SK, Sasaki R, Aggarwal BB (2002) Regulation of the activation of nuclear factor kappaB by mitochondrial respiratory function: evidence for the reactive oxygen species-dependent and -independent pathways. Antioxid Redox Signal 4:945–955

    CAS  PubMed  Google Scholar 

  • Hill BG, Benavides GA, Lancaster JR Jr, Ballinger S, Dell’Italia L, Jianhua Z et al (2012) Integration of cellular bioenergetics with mitochondrial quality control and autophagy. Biol Chem 393:1485–1512

    PubMed Central  CAS  PubMed  Google Scholar 

  • Horton TM, Petros JA, Heddi A, Shoffner J, Kaufman AE, Graham SD Jr et al (1996) Novel mitochondrial DNA deletion found in a renal cell carcinoma. Genes Chromosomes Cancer 15:95–101

    CAS  PubMed  Google Scholar 

  • Icard P, Lincet H (2012) A global view of the biochemical pathways involved in the regulation of the metabolism of cancer cells. Biochim Biophys Acta 1826:423–433

    CAS  PubMed  Google Scholar 

  • Imai S, Armstrong CM, Kaeberlein M, Guarente L (2000) Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403:795–800

    CAS  PubMed  Google Scholar 

  • Imanishi H, Hattori K, Wada R, Ishikawa K, Fukuda S, Takenaga K et al (2011) Mitochondrial DNA mutations regulate metastasis of human breast cancer cells. PLoS One 6:e23401

    PubMed Central  CAS  PubMed  Google Scholar 

  • Iommarini L, Calvaruso MA, Kurelac I, Gasparre G, Porcelli AM (2012) Complex I impairment in mitochondrial diseases and cancer: parallel roads leading to different outcomes. Int J Biochem Cell Biol 45:47–63

    PubMed  Google Scholar 

  • 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, Porcelli AM (2014) Different mtDNA mutations modify tumor progression in dependence of the degree of respiratory complex I impairment. Hum Mol Genet 23(6):1453–1466

    CAS  PubMed  Google Scholar 

  • Isaacs JS, Jung YJ, Mole DR, Lee S, Torres-Cabala C, Chung YL et al (2005) HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell 8:143–153

    CAS  PubMed  Google Scholar 

  • Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H et al (2008) ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science 320:661–664

    CAS  PubMed  Google Scholar 

  • Jandova J, Eshaghian A, Shi M, Li M, King LE, Janda J et al (2012a) Identification of an mtDNA mutation hot spot in UV-induced mouse skin tumors producing altered cellular biochemistry. J Invest Dermatol 132:421–428

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jandova J, Janda J, Sligh JE (2012b) Changes in mitochondrial DNA alter expression of nuclear encoded genes associated with tumorigenesis. Exp Cell Res 318:2215–2225

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kim JW, Tchernyshyov I, Semenza GL, Dang CV (2006) HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 3:177–185

    PubMed  Google Scholar 

  • Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV et al (2007) A “silent” polymorphism in the MDR1 gene changes substrate specificity. Science 315:525–528

    CAS  PubMed  Google Scholar 

  • Koivunen P, Lee S, Duncan CG, Lopez G, Lu G, Ramkissoon S et al (2012) Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation. Nature 483:484–488

    PubMed Central  CAS  PubMed  Google Scholar 

  • Komar AA (2007) Genetics. SNPs, silent but not invisible. Science 315:466–467

    CAS  PubMed  Google Scholar 

  • Kulawiec M, Owens KM, Singh KK (2009a) Cancer cell mitochondria confer apoptosis resistance and promote metastasis. Cancer Biol Ther 8:1378–1385

    CAS  PubMed  Google Scholar 

  • Kulawiec M, Owens KM, Singh KK (2009b) mtDNA G10398A variant in African-American women with breast cancer provides resistance to apoptosis and promotes metastasis in mice. J Hum Genet 54:647–654

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kurelac I, Lang M, Zuntini R, Calabrese C, Simone D, Vicario S et al (2011) Searching for a needle in the haystack: comparing six methods to evaluate heteroplasmy in difficult sequence context. Biotechnol Adv 30:363–371

    PubMed  Google Scholar 

  • Kurelac I, MacKay A, Lambros MB, Di Cesare E, Cenacchi G, Ceccarelli C et al (2013) Somatic complex I disruptive mitochondrial DNA mutations are modifiers of tumorigenesis that correlate with low genomic instability in pituitary adenomas. Hum Mol Genet 22:226–238

    CAS  PubMed  Google Scholar 

  • Kwong JQ, Henning MS, Starkov AA, Manfredi G (2007) The mitochondrial respiratory chain is a modulator of apoptosis. J Cell Biol 179:1163–1177

    PubMed Central  CAS  PubMed  Google Scholar 

  • Laloi-Michelin M, Meas T, Ambonville C, Bellanne-Chantelot C, Beaufils S, Massin P et al (2009) The clinical variability of maternally inherited diabetes and deafness is associated with the degree of heteroplasmy in blood leukocytes. J Clin Endocrinol Metab 94:3025–3030

    CAS  PubMed  Google Scholar 

  • Lang M, Sazzini M, Calabrese FM, Simone D, Boattini A, Romeo G et al (2012) Polymorphic NumtS trace human population relationships. Hum Genet 131:757–771

    PubMed  Google Scholar 

  • Larman TC, DePalma SR, Hadjipanayis AG, Protopopov A, Zhang J, Gabriel SB et al (2012) Spectrum of somatic mitochondrial mutations in five cancers. Proc Natl Acad Sci USA 109:14087–14091

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lascaro D, Castellana S, Gasparre G, Romeo G, Saccone C, Attimonelli M (2008) The RHNumtS compilation: features and bioinformatics approaches to locate and quantify Human NumtS. BMC Genomics 9:267

    PubMed Central  PubMed  Google Scholar 

  • Lebedeva MA, Eaton JS, Shadel GS (2009) Loss of p53 causes mitochondrial DNA depletion and altered mitochondrial reactive oxygen species homeostasis. Biochim Biophys Acta 1787:328–334

    PubMed Central  CAS  PubMed  Google Scholar 

  • Li Y, Weibing S, Liu H, Hongli J, Zhuosheng L, Yadong W et al (2008) Mitochondrial DNA from colorectal cancer cells promotes the malignant phenotype of NIH3T3 cells. Cell Biol Int 32:979–983

    CAS  PubMed  Google Scholar 

  • Liu J, Wang LD, Sun YB, Li EM, Xu LY, Zhang YP et al (2012) Deciphering the signature of selective constraints on cancerous mitochondrial genome. Mol Biol Evol 29:1255–1261

    CAS  PubMed  Google Scholar 

  • Liu VW, Wang Y, Yang HJ, Tsang PC, Ng TY, Wong LC et al (2003) Mitochondrial DNA variant 16189T > C is associated with susceptibility to endometrial cancer. Hum Mutat 22:173–174

    CAS  PubMed  Google Scholar 

  • Losman JA, Looper RE, Koivunen P, Lee S, Schneider RK, McMahon C et al (2013) (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science 339:1621–1625

    CAS  PubMed  Google Scholar 

  • Lozy F, Karantza V (2012) Autophagy and cancer cell metabolism. Semin Cell Dev Biol 23:395–401

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lu C, Thompson CB (2012) Metabolic regulation of epigenetics. Cell Metab 16:9–17

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lu J, Sharma LK, Bai Y (2009) Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis. Cell Res 19:802–815

    CAS  PubMed  Google Scholar 

  • Ma Y, Bai RK, Trieu R, Wong LJ (2010) Mitochondrial dysfunction in human breast cancer cells and their transmitochondrial cybrids. Biochim Biophys Acta 1797:29–37

    PubMed Central  CAS  PubMed  Google Scholar 

  • Mansfield KD, Guzy RD, Pan Y, Young RM, Cash TP, Schumacker PT et al (2005) Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metab 1:393–399

    PubMed Central  CAS  PubMed  Google Scholar 

  • Marucci G, Maresca A, Caporali L, Farnedi A, Betts CM, Morandi L et al (2013) Oncocytic glioblastoma: a glioblastoma showing oncocytic changes and increased mitochondrial DNA copy number. Hum Pathol 44:1867–1876

    CAS  PubMed  Google Scholar 

  • Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O et al (2006) p53 regulates mitochondrial respiration. Science 312:1650–1653

    CAS  PubMed  Google Scholar 

  • Memmott RM, Dennis PA (2009) Akt-dependent and -independent mechanisms of mTOR regulation in cancer. Cell Signal 21:656–664

    PubMed Central  CAS  PubMed  Google Scholar 

  • Minocherhomji S, Tollefsbol TO, Singh KK (2012) Mitochondrial regulation of epigenetics and its role in human diseases. Epigenetics 7:326–334

    PubMed Central  CAS  PubMed  Google Scholar 

  • Mizutani S, Miyato Y, Shidara Y, Asoh S, Tokunaga A, Tajiri T et al (2009) Mutations in the mitochondrial genome confer resistance of cancer cells to anticancer drugs. Cancer Sci 100:1680–1687

    CAS  PubMed  Google Scholar 

  • Moraes CT, Dey R, Barrientos A (2001) Transmitochondrial technology in animal cells. Methods Cell Biol 65:397–412

    CAS  PubMed  Google Scholar 

  • Morais R, Zinkewich-Peotti K, Parent M, Wang H, Babai F, Zollinger M (1994) Tumor-forming ability in athymic nude mice of human cell lines devoid of mitochondrial DNA. Cancer Res 54:3889–3896

    CAS  PubMed  Google Scholar 

  • Mullen AR, Wheaton WW, ** ES, Chen PH, Sullivan LB, Cheng T et al (2011) Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 481:385–388

    PubMed Central  PubMed  Google Scholar 

  • Nair J, Strand S, Frank N, Knauft J, Wesch H, Galle PR et al (2005) Apoptosis and age-dependant induction of nuclear and mitochondrial etheno-DNA adducts in Long-Evans Cinnamon (LEC) rats: enhanced DNA damage by dietary curcumin upon copper accumulation. Carcinogenesis 26:1307–1315

    CAS  PubMed  Google Scholar 

  • Naviaux RK (2008) Mitochondrial control of epigenetics. Cancer Biol Ther 7:1191–1193

    CAS  PubMed  Google Scholar 

  • Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC (2006) HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 3:187–197

    CAS  PubMed  Google Scholar 

  • Park JS, Sharma LK, Li H, **ang R, Holstein D, Wu J et al (2009) A heteroplasmic, not homoplasmic, mitochondrial DNA mutation promotes tumorigenesis via alteration in reactive oxygen species generation and apoptosis. Hum Mol Genet 18:1578–1589

    PubMed Central  CAS  PubMed  Google Scholar 

  • Partridge MA, Huang SX, Kibriya MG, Ahsan H, Davidson MM, Hei TK (2009) Environmental mutagens induced transversions but not transitions in regulatory region of mitochondrial DNA. J Toxicol Environ Health A 72:301–304

    CAS  PubMed  Google Scholar 

  • Payne BA, Wilson IJ, Yu-Wai-Man P, Coxhead J, Deehan D, Horvath R et al (2013) Universal heteroplasmy of human mitochondrial DNA. Hum Mol Genet 22:384–390

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pelicano H, Xu RH, Du M, Feng L, Sasaki R, Carew JS et al (2006) Mitochondrial respiration defects in cancer cells cause activation of Akt survival pathway through a redox-mediated mechanism. J Cell Biol 175:913–923

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pereira L, Freitas F, Fernandes V, Pereira JB, Costa MD, Costa S et al (2009) The diversity present in 5140 human mitochondrial genomes. Am J Hum Genet 84:628–640

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pereira L, Soares P, Maximo V, Samuels DC (2012) Somatic mitochondrial DNA mutations in cancer escape negative selection and high pathogenicity mutations lead to the oncocytic phenotype: pathogenicity analysis of reported somatic mtDNA mutations in tumors. BMC Cancer 12:53

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pesole G, Allen JF, Lane N, Martin W, Rand DM, Schatz G et al (2012) The neglected genome. EMBO Rep 13:473–474

    PubMed Central  CAS  PubMed  Google Scholar 

  • Petros JA, Baumann AK, Ruiz-Pesini E, Amin MB, Sun CQ, Hall J et al (2005) mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci USA 102:719–724

    PubMed Central  CAS  PubMed  Google Scholar 

  • Petruzzella V, Carrozzo R, Calabrese C, Dell’Aglio R, Trentadue R, Piredda R et al (2012) Deep sequencing unearths nuclear mitochondrial sequences under Leber’s hereditary optic neuropathy-associated false heteroplasmic mitochondrial DNA variants. Hum Mol Genet 21:3753–3764

    CAS  PubMed  Google Scholar 

  • Picardi E, Pesole G (2012) Mitochondrial genomes gleaned from human whole-exome sequencing. Nat Methods 9:523–524

    CAS  PubMed  Google Scholar 

  • Polyak K, Li Y, Zhu H, Lengauer C, Willson JK, Markowitz SD et al (1998) Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat Genet 20:291–293

    CAS  PubMed  Google Scholar 

  • Porcelli AM, Ghelli A, Ceccarelli C, Lang M, Cenacchi G, Capristo M et al (2010) The genetic and metabolic signature of oncocytic transformation implicates HIF1alpha destabilization. Hum Mol Genet 19:1019–1032

    CAS  PubMed  Google Scholar 

  • Raimundo N, Song L, Shutt TE, McKay SE, Cotney J, Guan MX et al (2012) Mitochondrial stress engages E2F1 apoptotic signaling to cause deafness. Cell 148:716–726

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ray PD, Huang BW, Tsuji Y (2012) Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 24:981–990

    PubMed Central  CAS  PubMed  Google Scholar 

  • Rossi ED, Martini M, Straccia P, Raffaelli M, Pennacchia I, Marrucci E et al (2013) The cytologic category of oncocytic (Hurthle) cell neoplasm mostly includes low-risk lesions at histology: an institutional experience. Eur J Endocrinol 169:649–655

    CAS  PubMed  Google Scholar 

  • Rossignol R, Faustin B, Rocher C, Malgat M, Mazat JP, Letellier T (2003) Mitochondrial threshold effects. Biochem J 370:751–762

    PubMed Central  CAS  PubMed  Google Scholar 

  • Rubino F, Piredda R, Calabrese FM, Simone D, Lang M, Calabrese C et al (2012) HmtDB, a genomic resource for mitochondrion-based human variability studies. Nucleic Acids Res 40:D1150–D1159

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ruiz-Pesini E, Mishmar D, Brandon M, Procaccio V, Wallace DC (2004) Effects of purifying and adaptive selection on regional variation in human mtDNA. Science 303:223–226

    CAS  PubMed  Google Scholar 

  • Salas A, Yao YG, Macaulay V, Vega A, Carracedo A, Bandelt HJ (2005) A critical reassessment of the role of mitochondria in tumorigenesis. PLoS Med 2:e296

    PubMed Central  PubMed  Google Scholar 

  • Samuels DC, Han L, Li J, Quanghu S, Clark TA, Shyr Y et al (2013) Finding the lost treasures in exome sequencing data. Trends Genet 29:593–599

    PubMed Central  CAS  PubMed  Google Scholar 

  • Santidrian AF, Matsuno-Yagi A, Ritland M, Seo BB, LeBoeuf SE, Gay LJ et al (2013) Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression. J Clin Invest 123:1068–1081

    PubMed Central  CAS  PubMed  Google Scholar 

  • Savagner F, Franc B, Guyetant S, Rodien P, Reynier P, Malthiery Y (2001) Defective mitochondrial ATP synthesis in oxyphilic thyroid tumors. J Clin Endocrinol Metab 86:4920–4925

    CAS  PubMed  Google Scholar 

  • Schon EA, DiMauro S, Hirano M (2012) Human mitochondrial DNA: roles of inherited and somatic mutations. Nat Rev Genet 13:878–890

    PubMed Central  CAS  PubMed  Google Scholar 

  • Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD et al (2005) Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell 7:77–85

    CAS  PubMed  Google Scholar 

  • Semenza GL, Roth PH, Fang HM, Wang GL (1994) Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J Biol Chem 269:23757–23763

    CAS  PubMed  Google Scholar 

  • Sharma LK, Fang H, Liu J, Vartak R, Deng J, Bai Y (2011) Mitochondrial respiratory complex I dysfunction promotes tumorigenesis through ROS alteration and AKT activation. Hum Mol Genet 20:4605–4616

    PubMed Central  CAS  PubMed  Google Scholar 

  • Shay JW, Werbin H (1987) Are mitochondrial DNA mutations involved in the carcinogenic process? Mutat Res 186:149–160

    CAS  PubMed  Google Scholar 

  • Shen YH, Wang XL, Wilcken DE (1998) Nitric oxide induces and inhibits apoptosis through different pathways. FEBS Lett 433:125–131

    CAS  PubMed  Google Scholar 

  • Shidara Y, Yamagata K, Kanamori T, Nakano K, Kwong JQ, Manfredi G et al (2005) Positive contribution of pathogenic mutations in the mitochondrial genome to the promotion of cancer by prevention from apoptosis. Cancer Res 65:1655–1663

    CAS  PubMed  Google Scholar 

  • Shock LS, Thakkar PV, Peterson EJ, Moran RG, Taylor SM (2011) DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria. Proc Natl Acad Sci USA 108:3630–3635

    PubMed Central  CAS  PubMed  Google Scholar 

  • Silbergeld DL, Mayberg MR, Berger MS, Ali-Osman F, Kelly WA, Shaw CM (1993) Pituitary oncocytomas: clinical features, characteristics in cell culture, and treatment recommendations. J Neurooncol 16:39–46

    CAS  PubMed  Google Scholar 

  • Simone D, Calabrese FM, Lang M, Gasparre G, Attimonelli M (2011) The reference human nuclear mitochondrial sequences compilation validated and implemented on the UCSC genome browser. BMC Genomics 12:517

    PubMed Central  PubMed  Google Scholar 

  • Singh KK, Ayyasamy V, Owens KM, Koul MS, Vujcic M (2009) Mutations in mitochondrial DNA polymerase-gamma promote breast tumorigenesis. J Hum Genet 54:516–524

    PubMed Central  CAS  PubMed  Google Scholar 

  • Skonieczna K, Malyarchuk BA, Grzybowski T (2012) The landscape of mitochondrial DNA variation in human colorectal cancer on the background of phylogenetic knowledge. Biochim Biophys Acta 1825:153–159

    CAS  PubMed  Google Scholar 

  • Smiraglia DJ, Kulawiec M, Bistulfi GL, Gupta SG, Singh KK (2008) A novel role for mitochondria in regulating epigenetic modification in the nucleus. Cancer Biol Ther 7:1182–1190

    PubMed Central  CAS  PubMed  Google Scholar 

  • Smolkova K, Jezek P (2012) The role of mitochondrial NADPH-dependent isocitrate dehydrogenase in cancer cells. Int J Cell Biol 2012:273947

    PubMed Central  PubMed  Google Scholar 

  • Smolkova K, Plecita-Hlavata L, Bellance N, Benard G, Rossignol R, Jezek P (2011) Waves of gene regulation suppress and then restore oxidative phosphorylation in cancer cells. Int J Biochem Cell Biol 43:950–968

    CAS  PubMed  Google Scholar 

  • St John JC, Facucho-Oliveira J, Jiang Y, Kelly R, Salah R (2010) Mitochondrial DNA transmission, replication and inheritance: a journey from the gamete through the embryo and into offspring and embryonic stem cells. Hum Reprod Update 16:488–509

    CAS  PubMed  Google Scholar 

  • Stafford P, Chen-Quin EB (2010) The pattern of natural selection in somatic cancer mutations of human mtDNA. J Hum Genet 55:605–612

    CAS  PubMed  Google Scholar 

  • Sun W, Zhou S, Chang SS, McFate T, Verma A, Califano JA (2009) Mitochondrial mutations contribute to HIF1alpha accumulation via increased reactive oxygen species and up-regulated pyruvate dehydrogenease kinase 2 in head and neck squamous cell carcinoma. Clin Cancer Res 15:476–484

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tallini G (1998) Oncocytic tumours. Virchows Arch 433:5–12

    CAS  PubMed  Google Scholar 

  • Tang S, Huang T (2010) Characterization of mitochondrial DNA heteroplasmy using a parallel sequencing system. Biotechniques 48:287–296

    CAS  PubMed  Google Scholar 

  • Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D et al (2002) Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet 30:406–410

    CAS  PubMed  Google Scholar 

  • Torroni A, Achilli A, Macaulay V, Richards M, Bandelt HJ (2006) Harvesting the fruit of the human mtDNA tree. Trends Genet 22:339–345

    CAS  PubMed  Google Scholar 

  • Tuppen HA, Blakely EL, Turnbull DM, Taylor RW (2010) Mitochondrial DNA mutations and human disease. Biochim Biophys Acta 1797:113–128

    CAS  PubMed  Google Scholar 

  • van Oven M, Kayser M (2009) Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum Mutat 30:E386–E394

    PubMed  Google Scholar 

  • Vogel RO, Smeitink JA, Nijtmans LG (2007) Human mitochondrial complex I assembly: a dynamic and versatile process. Biochim Biophys Acta 1767:1215–1227

    CAS  PubMed  Google Scholar 

  • Wallace DC (2012) Mitochondria and cancer. Nat Rev Cancer 12:685–698

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wallace DC (1999) Mitochondrial diseases in man and mouse. Science 283:1482–1488

    CAS  PubMed  Google Scholar 

  • Wallace DC (2005) A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 39:359–407

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wang PY, Ma W, Park JY, Celi FS, Arena R, Choi JW et al (2013) Increased oxidative metabolism in the Li-Fraumeni syndrome. N Engl J Med 368:1027–1032

    PubMed Central  CAS  PubMed  Google Scholar 

  • Warburg O (1956) On respiratory impairment in cancer cells. Science 124:269–270

    CAS  PubMed  Google Scholar 

  • Warburg O, Posener K, Negelein E (1924) Uber den Stoffwechsel der Carcinomzelle. Biochem Zeitschr 152:309–344

    CAS  Google Scholar 

  • Ward PS, Thompson CB (2012) Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell 21:297–308

    PubMed Central  CAS  PubMed  Google Scholar 

  • Weinberg F, Hamanaka R, Wheaton WW, Weinberg S, Joseph J, Lopez M et al (2010) Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci USA 107:8788–8793

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB (2009) ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324:1076–1080

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK et al (2008) Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci USA 105:18782–18787

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wise DR, Ward PS, Shay JE, Cross JR, Gruber JJ, Sachdeva UM et al (2011) Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of alpha-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci USA 108:19611–19616

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wiseman H, Halliwell B (1996) Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem J 313(Pt 1):17–29

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wong LJ, Boles RG (2005) Mitochondrial DNA analysis in clinical laboratory diagnostics. Clin Chim Acta 354:1–20

    CAS  PubMed  Google Scholar 

  • **ao M, Yang H, Xu W, Ma S, Lin H, Zhu H et al (2012) Inhibition of alpha-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev 26:1326–1338

    PubMed Central  CAS  PubMed  Google Scholar 

  • Yao YG, Salas A, Logan I, Bandelt HJ (2009) mtDNA data mining in GenBank needs surveying. Am J Hum Genet 85:929–933, author reply 33

    PubMed Central  CAS  PubMed  Google Scholar 

  • Yen HC, Tang YC, Chen FY, Chen SW, Majima HJ (2005) Enhancement of cisplatin-induced apoptosis and caspase 3 activation by depletion of mitochondrial DNA in a human osteosarcoma cell line. Ann N Y Acad Sci 1042:516–522

    CAS  PubMed  Google Scholar 

  • Yu M (2012) Somatic mitochondrial DNA mutations in human cancers. Adv Clin Chem 57:99–138

    CAS  PubMed  Google Scholar 

  • Zaragoza MV, Fass J, Diegoli M, Lin D, Arbustini E (2010) Mitochondrial DNA variant discovery and evaluation in human Cardiomyopathies through next-generation sequencing. PLoS One 5:e12295

    PubMed Central  PubMed  Google Scholar 

  • Zhou S, Kachhap S, Sun W, Wu G, Chuang A, Poeta L et al (2007) Frequency and phenotypic implications of mitochondrial DNA mutations in human squamous cell cancers of the head and neck. Proc Natl Acad Sci USA 104:7540–7545

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zu XL, Guppy M (2004) Cancer metabolism: facts, fantasy, and fiction. Biochem Biophys Res Commun 313:459–465

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical and Surgical Sciences, Medical Genetics, University Hospital S.Orsola-Malpighi, University of Bologna, via Massarenti 9, 40138, Bologna, Italy

    Ivana Kurelac, Michele Vidone, Giulia Girolimetti, Claudia Calabrese & Giuseppe Gasparre

  2. Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna, Via Massarenti 11, Bologna, Italy

    Giuseppe Gasparre

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  1. Ivana Kurelac
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  1. Inst. of Veterinary Physiology and Bioch, Justus-Liebig-University of Giessen, Gießen, Hessen, Germany

    Sybille Mazurek

  2. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden

    Maria Shoshan

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Kurelac, I., Vidone, M., Girolimetti, G., Calabrese, C., Gasparre, G. (2015). Mitochondrial Mutations in Cancer Progression: Causative, Bystanders, or Modifiers of Tumorigenesis?. In: Mazurek, S., Shoshan, M. (eds) Tumor Cell Metabolism. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1824-5_10

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