Abstract
Mitochondria are a major focus of research in cancer due to their critical role in tumor physiology and metabolism. Metabolic remodeling is observed in tumor cells, often resulting in increased glycolytic activity, which serves for the generation of adenosine triphosphate (ATP), and as hubs for biosynthesis of key metabolites essential for cancer cell growth and proliferation. Mitochondria, thus, appear as a critical nexus in cancer metabolic alterations. Not only increased overexpression of oncogenes leads to altered mitochondrial respiration due to remodeling of mitochondrial gene expression and substrate channeling, but also particular mutations in components of the respiratory chain trigger an upstream feedback mechanism which also leads to metabolic reshaping in cancer cells. Mitochondrial respiration can thus be controlled by intrinsic and extrinsic mechanisms in cancer cells, which ultimately translates into different abilities to generate mitochondrial ATP. Altered mitochondrial structures and processes can be a target for chemotherapeutics, which are increasingly being developed to specifically target mitochondria in tumors. The present chapter reviews current knowledge on regulation of mitochondrial respiration and overall metabolism and how these specific alterations in the cell powerhouse can be used to eliminate tumors.
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References
Abril J, De Heredia ML, González L, Clèries R, Nadal M, Condom E, Aguiló F, Gómez-Zaera M, Nunes V (2008) Altered expression of 12S/MT-RNR1, MT-CO2/COX2, and MT-ATP6 mitochondrial genes in prostate cancer. Prostate 68(10):1086–1096. http://www.ncbi.nlm.nih.gov/pubmed/18409190
Akiyoshi T, Matzno S, Sakai M, Okamura N, Matsuyama K (2009) The potential of vitamin K3 as an anticancer agent against breast cancer that acts via the mitochondria-related apoptotic pathway. Cancer Chemother Pharmacol 65(1):143–150. http://www.ncbi.nlm.nih.gov/pubmed/19449007
Alberola-Ila J, Hernández-Hoyos G (2003) The Ras/MAPK cascade and the control of positive selection. Immunol Rev 191:79–96. http://www.ncbi.nlm.nih.gov/pubmed/12614353
Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) Molecular biology of the cell, 4th edn. Molecular biology. Garland Science, New York. http://www.amazon.com/Molecular-Biology-Fourth-Bruce-Alberts/dp/0815332181
Alimoghaddam K, Shariftabrizi A, Tavangar SM, Sanaat Z, Rostami S, Jahani M, Ghavamzadeh A (2006) Anti-leukemic and anti-angiogenesis efficacy of arsenic trioxide in new cases of acute promyelocytic leukemia. Leukemia lymphoma. Vol. 47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16321832
Alirol E, Martinou JC (2006) Mitochondria and cancer: is there a morphological connection? Oncogene 25(34):4706–4716. http://www.ncbi.nlm.nih.gov/pubmed/16892084
Anastasiou D, Poulogiannis G, Asara JM, Boxer MB, Jiang J-K, Shen M, Bellinger G et al (2011) Inhibition of pyruvate kinase m2 by reactive oxygen species contributes to cellular antioxidant responses. Science 1278(2011):1278–1283. doi:10.5061/dryad.bp23483h. http://stke.sciencemag.org/cgi/content/abstract/sci;334/6060/1278
Armstrong JS (2007) Mitochondrial medicine: pharmacological targeting of mitochondria in disease. Br J Pharmacol 151(8):1154–1165. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2189819&tool=pmcentrez&rendertype=abstract
Arrington DD, Van Vleet TR, Schnellmann RG (2006) Calpain 10: a mitochondrial calpain and its role in calcium-induced mitochondrial dysfunction. Am J Physiol Cell Physiol 291(6):C1159–C1171. http://www.ncbi.nlm.nih.gov/pubmed/16790502
Assaily W, Rubinger DA, Wheaton K, Lin Y, Ma W, Xuan W, Brown-Endres L, Tsuchihara K, Mak TW, Benchimol S (2011) ROS-mediated P53 induction of Lpin1 regulates fatty acid oxidation in response to nutritional stress. Mol Cell 44(3):491–501. doi:10.1016/j.molcel.2011.08.038. http://www.ncbi.nlm.nih.gov/pubmed/22055193
Baracca A, Chiaradonna F, Sgarbi G, Solaini G, Alberghina L, Lenaz G (2010) Mitochondrial complex I decrease is responsible for bioenergetic dysfunction in K-ras transformed cells. Biochim Biophys Acta 1797(2):314–323. http://www.ncbi.nlm.nih.gov/pubmed/19931505
Barreto MC, Pinto RE, Arrabaça JD, Pavão ML (2003) Inhibition of mouse liver respiration by Chelidonium majus isoquinoline alkaloids. Toxicol Lett 146(1):37–47. http://linkinghub.elsevier.com/retrieve/pii/S0378427403003576
Barthel A, Okino ST, Liao J, Nakatani K, Li J, Whitlock JP, Roth RA (1999) Regulation of GLUT1 gene transcription by the serine/threonine kinase Akt1. J Biol Chem 274(29):20281–20286. http://www.ncbi.nlm.nih.gov/pubmed/10400647
Behrend L, Henderson G, Zwacka RM (2003) Reactive oxygen species in oncogenic transformation. Biochem Soc Trans 31(Pt 6):1441–1444. http://www.ncbi.nlm.nih.gov/pubmed/14641084
Benard G, Bellance N, James D, Parrone P, Fernandez H, Letellier T, Rossignol R (2007) Mitochondrial bioenergetics and structural network organization. J Cell Sci 120(Pt 5):838–848. http://www.ncbi.nlm.nih.gov/pubmed/17298981
Benard G, Bellance N, Jose C, Melser S, Nouette-Gaulain K, Rossignol R (2010) Multi-site control and regulation of mitochondrial energy production. Biochim Biophys Acta 1797(6–7):698–709. http://www.ncbi.nlm.nih.gov/pubmed/20226160
Bensaad K, Tsuruta A, Selak MA, Vidal MNC, Nakano K, Bartrons R, Gottlieb E, Vousden KH (2006) TIGAR, a P53-inducible regulator of glycolysis and apoptosis. Cell 126(1):107–120. http://eprints.gla.ac.uk/23551/
Berardi MJ, Fantin VR (2011) Survival of the fittest: metabolic adaptations in cancer. Curr Opin Genet Dev 21(1):59–66. http://www.ncbi.nlm.nih.gov/pubmed/21112206
Bernal SD, Lampidis TJ, McIsaac RM, Chen LB (1983) Anticarcinoma activity in vivo of rhodamine 123, a mitochondrial-specific dye. Science 222(4620):169–172. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve=PubMed=Citationlist_uids=6623064
Berridge MV, Herst PM, Tan AS (2010) Metabolic flexibility and cell hierarchy in metastatic cancer. Mitochondrion 10(6):584–588. http://www.ncbi.nlm.nih.gov/pubmed/20709626
Biasutto L, Mattarei A, Marotta E, Bradaschia A, Sassi N, Garbisa S, Zoratti M, Paradisi C (2008) Development of mitochondria-targeted derivatives of resveratrol. Bioorg Med Chem Lett 18(20):5594–5597. http://www.ncbi.nlm.nih.gov/pubmed/18823777
Blandino G, Valerio M, Cioce M, Mori F, Casadei L, Pulito C, Sacconi A et al (2012) Metformin elicits anticancer effects through the sequential modulation of DICER and c-MYC. Nature Commun 3(May):865. doi:10.1038/ncomms1859. http://www.nature.com/doifinder/10.1038/ncomms1859
Bo H, Jiang N, Ma G, Qu J, Zhang G, Cao D, Wen L, Liu S, Ji LL, Zhang Y (2008) Regulation of mitochondrial uncoupling respiration during exercise in rat heart: role of reactive oxygen species (ROS) and uncoupling protein 2. Free Radic Biol Med 44(7):1373–1381. http://www.ncbi.nlm.nih.gov/pubmed/18226608
Bogliolo M, Borghini S, Abbondandolo A, Degan P (2002) Alternative metabolic pathways for energy supply and resistance to apoptosis in fanconi anaemia. Mutagenesis 17(1):25–30
Bonora E, Porcelli AM, Gasparre G, Biondi A, Ghelli A, Carelli V, Baracca A et al (2006) Defective oxidative phosphorylation in thyroid oncocytic carcinoma is associated with pathogenic mitochondrial dna mutations affecting complexes I and III. Cancer Res 66(12):6087–6096. http://www.ncbi.nlm.nih.gov/pubmed/16778181
Bonuccelli G, Whitaker-Menezes D, Castello-Cros R, Pavlides S, Pestell RG, Fatatis A, Witkiewicz AK et al (2010) The reverse Warburg effect: glycolysis inhibitors prevent the tumor promoting effects of caveolin-1 deficient cancer associated fibroblasts. Cell Cycle Georgetown Tex 9(10):1960–1971. http://www.ncbi.nlm.nih.gov/pubmed/20495363
Bosch-Presegué L, Vaquero A (2011) The dual role of sirtuins in cancer. Genes Cancer 2(6):648–662. doi:10.1177/1947601911417862. http://www.ncbi.nlm.nih.gov/pubmed/21941620
Boutros J, Almasan A (2009) Combining 2-deoxy-D-glucose with electron transport chain blockers: a double-edged sword. Cancer Biol Ther 8(13):1237–1238. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2923584&tool=pmcentrez&rendertype=abstract
Boxer RB, Jang JW, Sintasath L, Chodosh LA (2004) Lack of sustained regression of c-MYC-induced mammary adenocarcinomas following brief or prolonged MYC inactivation. Cancer Cell 6(6):577–586. http://www.ncbi.nlm.nih.gov/pubmed/15607962
Brandon M, Baldi P, Wallace DC (2006) Mitochondrial mutations in cancer. Oncogene 25:4647–4662. doi:10.1038/sj.onc.1209607. http://www.nature.com/onc/journal/v25/n34/pdf/1209607a.pdf
Britten CD, Rowinsky EK, Baker SD, Weiss GR, Smith L, Stephenson J, Rothenberg M et al (2000) A phase I and pharmacokinetic study of the mitochondrial-specific rhodacyanine dye analog MKT 077. Clin Cancer Res 6:42–49
Brière J-J, Favier J, Gimenez-Roqueplo A-P, Rustin P (2006) Tricarboxylic acid cycle dysfunction as a cause of human diseases and tumor formation. Am J Physiol Cell Physiol 291(6):C1114–C1120. http://www.ncbi.nlm.nih.gov/pubmed/16760265
Brown AJ (2007) Cholesterol, statins and cancer. Clin Exp Pharmacol Physiol 34(3):135–141. http://www.ncbi.nlm.nih.gov/pubmed/17250629
Bulteau A-L, Bayot A (2011) Mitochondrial proteases and cancer. Biochim Biophys Acta 1807(6):595–601. http://www.ncbi.nlm.nih.gov/pubmed/21194520
Burnichon N, Brière J-J, Libé R, Vescovo L, Rivière J, Tissier F, Jouanno E et al (2010) SDHA is a tumor suppressor gene causing paraganglioma. Hum Mol Genet 19(15):3011–3020. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2901140&tool=pmcentrez&rendertype=abstract
Buzzai M, Bauer DE, Jones RG, Deberardinis RJ, Hatzivassiliou G, Elstrom RL, Thompson CB (2005) The glucose dependence of Akt-transformed cells can be reversed by pharmacologic activation of fatty acid beta-oxidation. Oncogene 24(26):4165–4173. http://www.ncbi.nlm.nih.gov/pubmed/15806154
Cadd VA, Hogg PJ, Harris AL, Feller SM (2006) Molecular profiling of signalling proteins for effects induced by the anti-cancer compound GSAO with 400 antibodies. BMC Cancer 6:155. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1550423&tool=pmcentrez&rendertype=abstract
Cadenas E (2004) Mitochondrial free radical production and cell signaling. Mol Aspects Med 25(1–2):17–26. http://www.ncbi.nlm.nih.gov/pubmed/15051313
Cairns R, Papandreou I, Denko N (2006) Overcoming physiologic barriers to cancer treatment by molecularly targeting the tumor microenvironment. Mol Cancer Res 4(2):61–70. http://www.ncbi.nlm.nih.gov/pubmed/16513837
Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P, Auwerx J (2009) AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 458(7241):1056–1060. http://www.ncbi.nlm.nih.gov/pubmed/19262508
Cao X, Fang L, Gibbs S, Huang Y, Dai Z, Wen P, Zheng X, Sadee W, Sun D (2007) Glucose uptake inhibitor sensitizes cancer cells to daunorubicin and overcomes drug resistance in hypoxia. Cancer Chemother Pharmacol 59(4):495–505. doi:10.1007/s00280–006-0291–9. http://www.ncbi.nlm.nih.gov/pubmed/16906425
Cao X, Jia G, Zhang T, Yang M, Wang B, Wassenaar PA, Cheng H, Knopp MV, Sun D (2008) Non-invasive MRI tumor imaging and synergistic anticancer effect of HSP90 inhibitor and glycolysis inhibitor in RIP1-Tag2 transgenic pancreatic tumor model. Cancer Chemother Pharmacol 62(6):985–994. http://www.ncbi.nlm.nih.gov/pubmed/18253734
Capaldi RA, Halphen DG, Zhang YZ, Yanamura W (1988) Complexity and tissue specificity of the mitochondrial respiratory chain. J Bioenerg Biomembr 20(3):291–311
Capparelli C, Whitaker-Menezes D, Guido C, Balliet R, Timothy G, Howell A, Sneddon S et al (2012) CTGF drives autophagy, glycolysis and senescence in cancer-associated fibroblasts via HIF1 activation, metabolically promoting tumor growth. Cell Cycle 11(12):2272–2284
Cárdenas-Navia LI, Mace D, Richardson RA, Wilson DF, Shan S, Dewhirst MW (2008) The pervasive presence of fluctuating oxygenation in tumors. Cancer Res 68(14):5812–5819. http://www.ncbi.nlm.nih.gov/pubmed/18632635
Cervera AM, Apostolova N, Crespo FL, Mata M, McCreath KJ (2008) Cells silenced for SDHB expression display characteristic features of the tumor phenotype. Cancer Res 68(11):4058–4067. http://www.ncbi.nlm.nih.gov/pubmed/18519664
Chao LC, Tontonoz P (2012) SIRT1 regulation—it ain’t all NAD. Mol Cell 45(1):9–11. doi:10.1016/j.molcel.2011.12.017. http://linkinghub.elsevier.com/retrieve/pii/S1097276511009907
Chatterjee A, Dasgupta S, Sidransky D (2011) Mitochondrial subversion in cancer. Cancer Prev Res (Phila) 4(5):638–654.http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3298745&tool=pmcentrez&rendertype=abstract
Chen ZX, Pervaiz S (2010) Involvement of cytochrome c oxidase subunits Va and Vb in the regulation of cancer cell metabolism by Bcl-2. Cell Death Differ 17(3):408–420. http://www.ncbi.nlm.nih.gov/pubmed/19834492
Chen K-H, Hsu W-M, Chiang C-C, Li Y-S (2003) Transforming growth factor-beta2 inhibition of corneal endothelial proliferation mediated by prostaglandin. Curr Eye Res 26(6):363–370. http://www.ncbi.nlm.nih.gov/pubmed/12868017
Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, Lesnefsky EJ (2003) production of reactive oxygen species by mitochondria: central role of complex III. J Biol Chem 278(38):36027–36031. http://www.ncbi.nlm.nih.gov/pubmed/12840017
Chen H, Chomyn A, Chan DC (2005) Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem 280(28):26185–26192. doi:10.1074/jbc.M503062200. http://www.ncbi.nlm.nih.gov/pubmed/15899901
Chen J-Q, Cammarata PR, Baines CP, Yager JD (2009) Regulation of mitochondrial respiratory chain biogenesis by estrogens/estrogen receptors and physiological, pathological and pharmacological implications. Biochim Biophys Acta 1793(10):1540–1570. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2744640&tool=pmcentrez&rendertype=abstract
Chen G, Wang F, Trachootham D, Huang P (2010) Preferential killing of cancer cells with mitochondrial dysfunction by natural compounds. Mitochondrion 10(6):614–625. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3085019&tool=pmcentrez&rendertype=abstract
Chen W-L, Kuo K-T, Chou T-Y, Chen C-L, Wang C-H, Wei Y-H, Wang L-S (2012) The role of cytochrome c oxidase subunit Va in nonsmall cell lung carcinoma cells: association with migration, invasion and prediction of distant metastasis. BMC Cancer 12(1):273. doi:10.1186/1471–2407-12–273. http://www.ncbi.nlm.nih.gov/pubmed/22748147
Cherk MH, Foo SS, Poon AMT, Knight SR, Murone C, Papenfuss AT, Sachinidis JI, Saunder THC, O’Keefe GJ, Scott AM (2006) Lack of correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in non-small cell lung cancer assessed by 18F-fluoromisonidazole and 18F-FDG PET. J Nucl Med 47(12):1921–1926. http://www.ncbi.nlm.nih.gov/pubmed/17138734
Chiaradonna F, Moresco RM, Airoldi C, Gaglio D, Palorini R, Nicotra F, Messa C, Alberghina L (2011) From cancer metabolism to new biomarkers and drug targets. Biotechnol Adv 30(1):30–51. doi:10.1016/j.biotechadv.2011.07.006. http://www.ncbi.nlm.nih.gov/pubmed/21802503
Choi WY, Kim G-Y, Lee WH, Choi YH (2008) Sanguinarine, a benzophenanthridine alkaloid, induces apoptosis in MDA-MB-231 human breast carcinoma cells through a reactive oxygen species-mediated mitochondrial pathway. Chemotherapy 54(4):279–287. http://www.ncbi.nlm.nih.gov/pubmed/18667818
Choi WY, Jin C-Y, Han MH, Kim G-Y, Kim ND, Lee WH, Kim S-K, Choi YH (2009) Sanguinarine sensitizes human gastric adenocarcinoma ags cells to TRAIL-mediated apoptosis via down-regulation of AKT and activation of caspase-3. Anticancer Res 29(11):4457–4465. http://www.ncbi.nlm.nih.gov/pubmed/20032392
Choo AY, Kim SG, Heiden MGV, Mahoney SJ, Vu H, Yoon S-O, Cantley LC, Blenis J (2010) Glucose addiction of TSC null cells is caused by failed mTORC1-dependent balancing of metabolic demand with supply. Mol Cell 38(4):487–499. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2896794&tool=pmcentrez&rendertype=abstract
Christofk HR, Heiden MGV, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC (2008) The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452(7184):230–233. doi:10.1038/nature06734. http://www.ncbi.nlm.nih.gov/pubmed/18337823
Cook CC, Kim A, Terao S, Gotoh A, Higuchi M (2012) Consumption of oxygen: a mitochondrial-generated progression signal of advanced cancer. Cell Death Dis 3(1):e258. doi:10.1038/cddis.2011.141. http://dx.doi.org/10.1038/cddis.2011.141
Cuezva JM, Krajewska M, De Heredia ML, Krajewski S, Santamaría G, Kim H, Zapata JM, Marusawa H, Chamorro M, Reed JC (2002) The bioenergetic signature of cancer: a marker of tumor progression. Cancer Res 62(22):6674–6681. http://www.ncbi.nlm.nih.gov/pubmed/12438266
Cuezva JM, Sánchez-Aragó M, Sala S, Blanco-Rivero A, Ortega AD (2007) A message emerging from development: the repression of mitochondrial beta-F1-ATPase expression in cancer. J Bioenerg Biomembr 39(3):259–265. http://www.ncbi.nlm.nih.gov/pubmed/17712532
Cuperus R, Leen R, Tytgat GAM, Caron HN, Van Kuilenburg ABP (2010) Fenretinide induces mitochondrial ROS and inhibits the mitochondrial respiratory chain in neuroblastoma. Cell Mol Life Sci 67(5):807–816. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2824117&tool=pmcentrez&rendertype=abstract
Czarnecka AM, Klemba A, Krawczyk T, Zdrozny M, Arnold RS, Bartnik E, Petros JA (2010) Mitochondrial NADH-dehydrogenase polymorphisms as sporadic breast cancer risk factor. Oncol Rep 23(2):531–535. http://www.ncbi.nlm.nih.gov/pubmed/20043118
Damm F, Bunke T, Thol F, Markus B, Wagner K, Göhring G, Schlegelberger B et al (2011) Prognostic implications and molecular associations of NADH dehydrogenase subunit 4 (ND4) mutations in acute myeloid leukemia. Leukemia 26(2):289–295. doi:10.1038/leu.2011.200. http://www.ncbi.nlm.nih.gov/pubmed/21826063
Dang CV (2010) Rethinking the Warburg effect with Myc micromanaging glutamine metabolism. Cancer Res 70(3):859–862. doi:10.1158/0008–5472.CAN-09–3556. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2818441&tool=pmcentrez&rendertype=abstract
Dang CV (2012) Links between metabolism and cancer. Genes Dev 26(9):877–890. doi:10.1101/gad.189365.112. http://www.ncbi.nlm.nih.gov/pubmed/22549953
Dang CV (2012) MYC on the path to cancer. Cell 149(1):22–35. doi:10.1016/j.cell.2012.03.003. http://linkinghub.elsevier.com/retrieve/pii/S0092867412002966
Dang CV, Kim J, Gao P, Yustein J (2008) The interplay between MYC and HIF in cancer. Nat Rev Cancer 8(1):51–56. http://www.ncbi.nlm.nih.gov/pubmed/18046334
Dang CV, Le A, Gao P (2009) MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clin Cancer Res 15(21):6479–6483. http://www.ncbi.nlm.nih.gov/pubmed/19861459
Dasgupta S, Hoque MO, Upadhyay S, Sidransky D (2008) Mitochondrial cytochrome B gene mutation promotes tumor growth in bladder cancer. Cancer Res 68(3):700–706. http://www.ncbi.nlm.nih.gov/pubmed/18245469
David CJ, Chen M, Assanah M, Canoll P, Manley JL (2010) HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 463(7279):364–368. http://www.ncbi.nlm.nih.gov/pubmed/20010808
Dayan F, Mazure NM, Brahimi-Horn MC, Pouysségur J (2008) A dialogue between the hypoxia-inducible factor and the tumor microenvironment. Cancer Microenviron 1(1):53–68. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2654353&tool=pmcentrez&rendertype=abstract
DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, Thompson CB (2007) Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci U S A 104(49):19345–19350. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2148292&tool=pmcentrez&rendertype=abstract
De Brito OM, Scorrano L (2008) Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 456(7222):605–610. http://www.ncbi.nlm.nih.gov/pubmed/19052620
Decaudin D, Marzo I, Brenner C, Kroemer G (1998) Mitochondria in chemotherapy-induced apoptosis: a prospective novel target of cancer therapy (review). Int J Oncol 12(1):141–152. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9454898
Dell’Antone P (2009) Targets of 3-bromopyruvate, a new, energy depleting, anticancer agent. Med Chem 5(6):491–496
Dell’ Antone P (2012) Energy metabolism in cancer cells: How to Explain the Warburg and Crabtree effects? Med Hypotheses 79(3):388–392. doi:10.1016/j.mehy.2012.06.002. http://www.ncbi.nlm.nih.gov/pubmed/22770870
Delmas D, Rébé C, Micheau O, Athias A, Gambert P, Grazide S, Laurent G, Latruffe N, Solary E (2004) Redistribution of CD95, DR4 and DR5 in rafts accounts for the synergistic toxicity of resveratrol and death receptor ligands in colon carcinoma cells. Oncogene 23(55):8979–8986. http://www.ncbi.nlm.nih.gov/pubmed/15480430
Deng C-X (2009) SIRT1, is it a tumor promoter or tumor suppressor? Int J Biol Sci 5(2):147–152. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2631220&tool=pmcentrez&rendertype=abstract
Denton RM, Randle PJ, Martin BR (1972) Stimulation by calcium ions of pyruvate dehydrogenase phosphate phosphatase. Biochem J 128:161–163
Denton RM, Richards DA, Chin JG (1978) Calcium ions and the regulation of NAD+ -linked isocitrate dehydrogenase from the mitochondria of rat heart and other tissues. Biochem J 176(3):899–906. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1186314&tool=pmcentrez&rendertype=abstract
Desler C, Marcker ML, Singh KK, Rasmussen LJ (2011) The importance of mitochondrial DNA in aging and cancer. J Aging Res 2011:407536. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3092560&tool=pmcentrez&rendertype=abstract
Desouki MM, Kulawiec M, Bansal S, Das GM, Singh KK (2005) Cross talk between mitochondria and superoxide generating NADPH oxidase in breast and ovarian tumors. Cancer Biol Ther 4(12):1367–1373. http://www.ncbi.nlm.nih.gov/pubmed/16294028
Dewhirst MW (2007) Intermittent hypoxia furthers the rationale for hypoxia-inducible factor-1 targeting. Cancer Res 67(3):854–855. http://www.ncbi.nlm.nih.gov/pubmed/17283112
Diano S, Horvath TL (2012) Mitochondrial uncoupling protein 2 (UCP2) in glucose and lipid metabolism. Trends Mol Med 18(1):52–8. doi:10.1016/j.molmed.2011.08.003. http://www.ncbi.nlm.nih.gov/pubmed/21917523
Dias N, Bailly C (2005) Drugs targeting mitochondrial functions to control tumor cell growth. Biochem Pharmacol 70(1):1–12. doi:10.1016/j.bcp.2005.03.021. http://www.ncbi.nlm.nih.gov/pubmed/15907809
Diaz-Ruiz R, Uribe-Carvajal S, Devin A, Rigoulet M (2009) Tumor cell energy metabolism and its common features with yeast metabolism. Biochim Biophys Acta 1796(2):252–265. http://www.ncbi.nlm.nih.gov/pubmed/19682552
Diaz-Ruiz R, Rigoulet M, Devin A (2011) The warburg and crabtree effects: on the origin of cancer cell energy metabolism and of yeast glucose repression. Biochim Biophys Acta 1807(6):568–576. http://www.ncbi.nlm.nih.gov/pubmed/20804724
Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ, Kulp AN, Qian D et al (2009) Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 458(7239):780–783. http://www.ncbi.nlm.nih.gov/pubmed/19194462
Dilda PJ, Hogg PJ (2007) Arsenical-based cancer drugs. Cancer Treat Rev 33(6):542–564. http://www.ncbi.nlm.nih.gov/pubmed/17624680
Dilda PJ, Ramsay EE, Corti A, Pompella A, Hogg PJ (2008) Metabolism of the tumor angiogenesis inhibitor 4-(N-(S-Glutathionylacetyl)amino)phenylarsonous acid. J Biol Chem 283(51):35428–35434. doi:10.1074/jbc.M804470200. http://www.ncbi.nlm.nih.gov/pubmed/18723877
Di Monte D, Ross D, Bellomo G, Eklöw L, Orrenius S (1984) Alterations in intracellular thiol homeostasis during the metabolism of menadione by isolated rat hepatocytes. Arch Biochem Biophys 235(2):334–342. http://view.ncbi.nlm.nih.gov/pubmed/6097182
Domenis R, Comelli M, Bisetto E, Mavelli I (2011) Mitochondrial bioenergetic profile and responses to metabolic inhibition in human hepatocarcinoma cell lines with distinct differentiation characteristics. J Bioenerg Biomembr 43(5):493–505. http://www.ncbi.nlm.nih.gov/pubmed/21882038
Don AS, Hogg PJ (2004) Mitochondria as cancer drug targets. Trends Mol Med 10(8):372–378. http://www.ncbi.nlm.nih.gov/pubmed/15310457
Don AS, Kisker O, Dilda P, Donoghue N, Zhao X, Decollogne S, Creighton B, Flynn E, Folkman J, Hogg PJ (2003) A peptide trivalent arsenical inhibits tumor angiogenesis by perturbing mitochondrial function in angiogenic endothelial cells. Cancer Cell 3(5):497–509. http://www.scopus.com/inward/record.url?eid=2-s2.0–0142010897&partnerID=40&md5=bfd334bfd89a8947881c1aa8e3511f60
Dong L-F, Swettenham E, Eliasson J, Wang X-F, Gold M, Medunic Y, Stantic M et al (2007) Vitamin E analogues inhibit angiogenesis by selective induction of apoptosis in proliferating endothelial cells: the role of oxidative stress. Cancer Res 67(24):11906–11913. http://www.ncbi.nlm.nih.gov/pubmed/18089821
Dong L-F, Freeman R, Liu J, Zobalova R, Marin-Hernandez A, Stantic M, Rohlena J et al (2009) Suppression of tumor growth in vivo by the mitocan alpha-tocopheryl succinate requires respiratory complex II. Clin Cancer Res 15(5):1593–1600. http://www.ncbi.nlm.nih.gov/pubmed/19223492.
Dong L-F, Jameson VJA, Tilly D, Prochazka L, Rohlena J, Valis K, Truksa J et al (2011) Mitochondrial targeting of α-tocopheryl succinate enhances its pro-apoptotic efficacy: a new paradigm for effective cancer therapy. Free Radic Biol Med 50(11):1546–1555. http://www.ncbi.nlm.nih.gov/pubmed/21402148.
Dos Santos MA, Borges JB, De Almeida DCCuri R (2004) Metabolism of the microregions of human breast cancer. Cancer Lett 216(2):243–248
Dromparis P, Sutendra G, Michelakis ED (2010) The role of mitochondria in pulmonary vascular remodeling. J Mol Med (Berl) 88(10):1003–1010. http://www.ncbi.nlm.nih.gov/pubmed/20734021
Dudkina NV, Kouril R, Peters K, Braun H-P, Boekema EJ (2010) Structure and function of mitochondrial supercomplexes. Biochim Biophys Acta 1797(6–7):664–670. http://www.ncbi.nlm.nih.gov/pubmed/20036212
Echtay KS, Brand MD (2007) 4-hydroxy-2-nonenal and uncoupling proteins: an approach for regulation of mitochondrial ROS production. Redox Rep 12(1):26–29. http://www.ncbi.nlm.nih.gov/pubmed/17263904
Edinger AL, Thompson CB (2002) Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake. Mol Biol Cell 13(7):2276–2288. http://www.molbiolcell.org/cgi/content/abstract/13/7/2276
Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR, Zhuang H et al (2004) Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 64(11):3892–3899. doi:10.1158/0008–5472.CAN-03–2904
Engelman JA, Chen L, Tan X, Crosby K, Guimaraes AR, Upadhyay R, Maira M et al (2008) Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 14(12):1351–1356. doi:10.1038/nm.1890. http://www.ncbi.nlm.nih.gov/pubmed/19029981
Estrela JM, Ortega A, Obrador E (2006) Glutathione in cancer biology and therapy. Crit Rev Clin Lab Sci 43(2):143–181. http://www.ncbi.nlm.nih.gov/pubmed/16517421
Fanciulli M, Valentini A, Bruno T, Citro G, Zupi G, Floridi A (1996) Effect of the antitumor drug lonidamine on glucose metabolism of adriamycin-sensitive and -resistant human breast cancer cells. Oncol Res 8(3):111–120
Fantin VR, Leder P (2004) F16, a mitochondriotoxic compound, triggers apoptosis or necrosis depending on the genetic background of the target carcinoma cell. Cancer Res 64(1):329–336. http://www.ncbi.nlm.nih.gov/pubmed/14729642
Feichtinger RG, Zimmermann F, Mayr JA, Neureiter D, Hauser-Kronberger C, Schilling FH, Jones N, Sperl W, Kofler B (2010) Low aerobic mitochondrial energy metabolism in poorly- or undifferentiated neuroblastoma. BMC Cancer 10(1):149. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2861660&tool=pmcentrez&rendertype=abstract
Feng S, Xiong L, Ji Z, Cheng W, Yang H (2012) Correlation between increased ND2 expression and demethylated displacement loop of mtDNA in colorectal cancer. Mol Med Rep 6(1)125–130. doi:10.3892/mmr.2012.870. http://www.ncbi.nlm.nih.gov/pubmed/22505229
Ferber EC, Peck B, Delpuech O, Bell GP, East P, Schulze A (2011) FOXO3a regulates reactive oxygen metabolism by inhibiting mitochondrial gene expression. Cell Death Differ 19(6):1–12. doi:10.1038/cdd.2011.179. http://dx.doi.org/10.1038/cdd.2011.179
Fernández-Vizarra E, Enríquez JA, Pérez-Martos A, Montoya J, Fernández-Silva P (2011) Tissue-specific differences in mitochondrial activity and biogenesis. Mitochondrion 11(1):207–213. http://www.ncbi.nlm.nih.gov/pubmed/20933104
Ferreira LMR (2010) Cancer metabolism: the warburg effect today. Exp Mol Pathol 89(3):372–380. http://www.ncbi.nlm.nih.gov/pubmed/20804748
Fiaschi T, Chiarugi P (2012) Oxidative stress, tumor microenvironment, and metabolic reprogramming: a diabolic liaison. Int J Cell Biol 2012:762825. doi:10.1155/2012/762825. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3361160&tool=pmcentrez&rendertype=abstract
Filomeni G, Cardaci S, Ferreira AMDC, Rotilio G, Ciriolo MR (2011) Metabolic oxidative stress elicited by the copper(II) complex [Cu(isaepy)2] triggers apoptosis in SH-SY5Y cells through the induction of the AMP-activated protein kinase/p38MAPK/p53 signalling axis: evidence for a combined use with 3-bromopyruvate in neur. Biochem J 437(3):443–453. doi:10.1042/BJ20110510. http://www.ncbi.nlm.nih.gov/pubmed/21548882
Fosslien E (2008) Cancer morphogenesis: role of mitochondrial failure. Ann Clin Lab Sci 38(4):307–329. http://www.ncbi.nlm.nih.gov/pubmed/18988924
Frezza C, Gottlieb E (2009) Mitochondria in cancer: not just innocent bystanders. Semin Cancer Biol 19(1):4–11. http://www.ncbi.nlm.nih.gov/pubmed/19101633
Fukuda R, Zhang H, Kim J, Shimoda L, Dang CV, Semenza GL (2007) HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell 129(1):111–122. http://www.ncbi.nlm.nih.gov/pubmed/17418790
Fulda S, Galluzzi L, Kroemer G (2010) Targeting mitochondria for cancer therapy. Nature Rev Drug Discov 9(6):447–464. doi:10.1038/nrd3137. http://www.ncbi.nlm.nih.gov/pubmed/20467424
Gaglio D, Soldati C, Vanoni M, Alberghina L, Chiaradonna F (2009) Glutamine deprivation induces abortive S-phase rescued by deoxyribonucleotides in K-Ras transformed fibroblasts. PLoS ONE 4(3):17. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2650790&tool=pmcentrez&rendertype=abstract
Gaglio D, Metallo CM, Gameiro PA, Hiller K, Danna LS, Balestrieri C, Alberghina L, Stephanopoulos G, Chiaradonna F (2011) Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth. Mol Syst Biol 7(523):523. doi:10.1038/msb.2011.56. http://www.nature.com/doifinder/10.1038/msb.2011.56
Gallagher EJ, LeRoith D (2011) Diabetes, cancer, and metformin: connections of metabolism and cell proliferation. Ann N Y Acad Sci 1243(1):54–68. doi:10.1111/j.1749–6632.2011.06285.x. http://www.ncbi.nlm.nih.gov/pubmed/22211893
Gasparre G, Porcelli AM, Bonora E, Pennisi LF, Toller M, Iommarini L, Ghelli A et al (2007) Disruptive mitochondrial DNA mutations in complex I subunits are markers of oncocytic phenotype in thyroid tumors. Proc Natl Acad Sci U S A 104(21):9001–9006. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1885617&tool=pmcentrez&rendertype=abstract
Gasparre G, Hervouet E, De Laplanche E, Demont J, Pennisi LF, Colombel M, Mège-Lechevallier F 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(7):986–995. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18156159
Gatenby RA, Gawlinski ET (2003) The glycolytic phenotype in carcinogenesis and tumor invasion: insights through mathematical models. Cancer Res 63(14):3847–3854. http://www.ncbi.nlm.nih.gov/pubmed/12873971
Gatenby RA, Gillies RJ (2007) Glycolysis in cancer: a potential target for therapy. Int J Biochem Cell Biol 39(7–8):1358–1366. http://www.ncbi.nlm.nih.gov/pubmed/17499003
Geschwind J-FH, Ko YH, Torbenson MS, Magee C, Pedersen PL (2002) Novel therapy for liver cancer: direct intraarterial injection of a potent inhibitor of ATP production. Cancer Res 62(14):3909–3913. http://www.ncbi.nlm.nih.gov/pubmed/12124317
Giannoni E, Bianchini F, Calorini L, Chiarugi P (2011) Cancer associated fibroblasts exploit reactive oxygen species through a proinflammatory signature leading to epithelial mesenchymal transition and stemness. Antioxid Redox Signal 14(12):2361–2371. http://www.ncbi.nlm.nih.gov/pubmed/21235356
Giralt A, Villarroya F (2012) SIRT3, a pivotal actor in mitochondrial functions: metabolism, cell death and aging. Biochem J 444(1):1–10. doi:10.1042/BJ20120030. http://www.ncbi.nlm.nih.gov/pubmed/22533670
Gledhill JR, Montgomery MG, Leslie AGW, Walker JE (2007) Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols. Proc Natl Acad Sci U S A 104(34):13632–13637. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1948022&tool=pmcentrez&rendertype=abstract
Gleiss B, Gogvadze V, Orrenius S, Fadeel B (2002) Fas-triggered phosphatidylserine exposure is modulated by intracellular ATP. FEBS Lett 519(1–3):153–158. http://www.ncbi.nlm.nih.gov/pubmed/12023035
Gnaiger E (2009) Capacity of oxidative phosphorylation in human skeletal muscle: new perspectives of mitochondrial physiology. Int J Biochem Cell Biol 41(10):1837–1845. http://www.ncbi.nlm.nih.gov/pubmed/19467914
Gogvadze V, Norberg E, Orrenius S, Zhivotovsky B (2010) Involvement of Ca2+ and ROS in alpha-tocopheryl succinate-induced mitochondrial permeabilization. Int J Cancer 127(8):1823–1832. doi:10.1002/ijc.25204. http://www.ncbi.nlm.nih.gov/pubmed/20104525
Gogvadze V, Zhivotovsky B, Orrenius S (2010) The warburg effect and mitochondrial stability in cancer cells. Mol Aspects Med 31(1):60–74. http://www.ncbi.nlm.nih.gov/pubmed/19995572
Gottlieb E, Tomlinson IPM (2005) Mitochondrial tumour suppressors: a genetic and biochemical update. Nat Rev Cancer 5(11):857–866. http://eprints.gla.ac.uk/23550/
Gough DJ, Corlett A, Schlessinger K, Wegrzyn J, Larner AC, Levy DE (2009) Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science 324(5935):1713–1716. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2840701&tool=pmcentrez&rendertype=abstract
Green DR, Chipuk JE (2006) p53 and metabolism: inside the TIGAR. Cell 126(1):30–32. doi:10.1016/j.cell.2006.06.032
Greiner EF, Guppy M, Brand K (1994) Glucose is essential for proliferation and the glycolytic enzyme induction that provokes a transition to glycolytic energy production. J Biol Chem 269(50):31484–31490. http://www.ncbi.nlm.nih.gov/pubmed/7989314
Guchelaar H, Vermes A, Vermes I, Haanen C (1997) Apoptosis: molecular mechanisms and implications for cancer chemotherapy. Pharm World Sci 19(3):119–125 [Erratum appears in Pharm World Sci 1997 Oct;19(5):253]
Gupta GP, Nguyen DX, Chiang AC, Bos PD, Kim JY, Nadal C, Gomis RR, Manova-Todorova K, Massagué J (2007) Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. Nature 446(7137):765–770. http://www.ncbi.nlm.nih.gov/pubmed/17429393
Gupta SC, Kannappan R, Reuter S, Kim JH, Aggarwal BB (2011) chemosensitization of tumors by resveratrol. Ann N Y Acad Sci 1215(1):150–160. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3060406&tool=pmcentrez&rendertype=abstract
Guzy RD, Sharma B, Bell E, Chandel NS, Schumacker PT (2008) Loss of the SdhB, but not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis. Mol Cell Biol 28(2):718–731. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2223429&tool=pmcentrez&rendertype=abstract
Ha T-K, Her N-G, Lee M-G, Ryu B-K, Lee J-H, Han J, Jeong S-I et al (2012) Caveolin-1 increases aerobic glycolysis in colorectal cancers by stimulating HMGA1-mediated GLUT3 transcription. Cancer Res 72(16):4097–5109. doi:10.1158/0008–5472.CAN-12–0448. http://www.ncbi.nlm.nih.gov/pubmed/22706202
Hackenbrock CR (1972) Energy-linked ultrastructural transformations in isolated liver mitochondria and mitoplasts. J Cell Biol 53(2):450–465. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2108731&tool=pmcentrez&rendertype=abstroact
Hajnóczky G, Csordás G, Das S, Garcia-Perez C, Saotome M, Roy SS, Yi M (2006) Mitochondrial calcium signalling and cell death: approaches for assessing the role of mitochondrial Ca2+ uptake in apoptosis. Cell Calcium 40(5–6):553–560. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2692319&tool=pmcentrez&rendertype=abstract
Hamanaka RB, Chandel NS (2010) Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends Biochem Sci 35(9):505–513. http://www.ncbi.nlm.nih.gov/pubmed/20430626
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70. doi:10.1007/s00262–010-0968–0. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3042096&tool=pmcentrez&rendertype=abstract
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. http://www.ncbi.nlm.nih.gov/pubmed/21376230
Hansford RG, Chappell JB.(1967) The effect of Ca2 + on the oxidation of glycerol phosphate by blowfly flight-muscle mitochondria. Biochem Biophys Res Commun 27(6):686–692. http://www.ncbi.nlm.nih.gov/pubmed/21376230http://www.ncbi.nlm.nih.gov/pubmed/4964598
Hatzivassiliou G, Zhao F, Bauer DE, Andreadis C, Shaw AN, Dhanak D, Hingorani SR, Tuveson DA, Thompson CB (2005) ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 8(4):311–321. http://www.ncbi.nlm.nih.gov/pubmed/16226706
He X, Cao X (2010) Identification of alternatively spliced GRIM-19 mRNA in kidney cancer tissues. J Hum Genet 55(8):507–511. doi:10.1038/jhg.2010.57. http://www.ncbi.nlm.nih.gov/pubmed/20505682
Heerdt BG, Halsey HK, Lipkin M, Cancer C, Augenlicht LH (1990) Expression of mitochondrial cytochrome c oxidase in human colonic cell differentiation, transformation, and risk for colonic cancer. Cancer Res 50(5):1596–1600
Hensen EF, Bayley J-P (2011) Recent advances in the genetics of SDH-related paraganglioma and pheochromocytoma. Fam Cancer 10(2):355–363. http://www.ncbi.nlm.nih.gov/pubmed/21082267
Hu X, Zhang X, Qiu S, Yu D, Lin S (2010) Biochemical and biophysical research communications salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells. Biochem Biophys Res Commun 398(1):62–67. doi:10.1016/j.bbrc.2010.06.033. http://dx.doi.org/10.1016/j.bbrc.2010.06.033
Huang Y, Peng J, Oberley LW, Domann FE (1997) Transcriptional inhibition of manganese superoxide dismutase (SOD2) gene expression by DNA methylation of the 5′ CpG island. Free Radic Biol Med 23(2):314–320. http://www.ncbi.nlm.nih.gov/pubmed/9199894
Hüttemann M, Lee I, Samavati L, Yu H, Doan JW (2007) Regulation of mitochondrial oxidative phosphorylation through cell signaling. Biochim Biophys Acta 722(1):43–50. http://linkinghub.elsevier.com/retrieve/pii/S0167488907002364
Hüttemann M, Lee I, Grossman LI, Doan JW, Sanderson TH (2012) Phosphorylation of mammalian cytochrome c and cytochrome c oxidase in the regulation of cell destiny: respiration, apoptosis, and human disease. Adv Exp Med Biol 748:237–64. doi:10.1007/978–1-4614–3573-0_10. http://www.ncbi.nlm.nih.gov/pubmed/22729861
Icard P, Poulain L, Lincet H (2012) Understanding the central role of citrate in the metabolism of cancer cells. Biochim Biophys Acta 1825(1):111–116. doi:10.1016/j.bbcan.2011.10.007. http://www.ncbi.nlm.nih.gov/pubmed/22101401
Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H, Nakada K, Honma Y, Hayashi J-I (2008) ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science 320(5876):661–664. http://www.ncbi.nlm.nih.gov/pubmed/18388260
Isidoro A, Martínez M, Fernández PL, Ortega AD, Santamaría G, Chamorro M, Reed JC, Cuezva JM (2004) Alteration of the bioenergetic phenotype of mitochondria is a hallmark of breast, gastric, lung and oesophageal cancer. Biochem J 378(Pt 1):17–20. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1223948&tool=pmcentrez&rendertype=abstract
Jain M, Arvanitis C, Chu K, Dewey W, Leonhardt E, Trinh M, Sundberg CD, Bishop JMichael, Felsher DW (2002) Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science 297(5578):102–104. http://www.ncbi.nlm.nih.gov/pubmed/12098700
Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, et al (1997) Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275(5297):218–220. http://www.sciencemag.org/cgi/doi/10.1126/science.275.5297.218
Jantova S, Cipak L, Letasiova S (2007) Berberine induces apoptosis through a mitochondrial/ caspase pathway in human promonocytic U937 cells. Toxicol In Vitro 21:25–31. doi:10.1016/j.tiv.2006.07.015
Jensen KS, Binderup T, Jensen KT, Therkelsen I, Borup R, Nilsson E, Multhaupt H et al (2011) FoxO3A promotes metabolic adaptation to hypoxia by antagonizing myc function. Eur Mol Biol Organ J 30(22):4554–4570. doi:10.1038/emboj.2011.323. http://www.ncbi.nlm.nih.gov/pubmed/21915097
Jia L, Yu W, Wang P, Sanders BG, Kline K (2008) In vivo and in vitro studies of anticancer actions of alpha-TEA for human prostate cancer cells. Prostate 68(8):849–860. doi:10.1002/pros.20750. http://www.ncbi.nlm.nih.gov/pubmed/18324647
Jung K, Seidel B, Rudolph B, Lein M, Cronauer MV, Henke W, Hampel G, Schnorr D, Loening SA (1997) antioxidant enzymes in malignant prostate cell lines and in primary cultured prostatic cells. Free Radic Biol Med 23(1):127–133. http://www.ncbi.nlm.nih.gov/pubmed/9165305
Kamp DW, Shacter E, Weitzman SA (2011) Chronic inflammation and cancer: the role of the mitochondria. Oncology (Williston Park) 25(5):400–410, 413. http://www.ncbi.nlm.nih.gov/pubmed/21710835
Kang J, Pervaiz S (2012) Mitochondria: redox metabolism and dysfunction. Biochem Res Int 2012: 896751. doi:10.1155/2012/896751. http://www.ncbi.nlm.nih.gov/pubmed/22593827
Kang BH, Plescia J, Dohi T, Rosa J, Doxsey SJ, Altieri DC (2007) Regulation of tumor cell mitochondrial homeostasis by an organelle-specific Hsp90 chaperone network. Cell 131(2):257–270. http://www.ncbi.nlm.nih.gov/pubmed/17956728
Kang BH, Plescia J, Song HY, Meli M, Colombo G, Beebe K, Scroggins B, Neckers L, Altieri DC (2009) Combinatorial drug design targeting multiple cancer signaling networks controlled by mitochondrial Hsp90. J Clin Invest 119(3):454–464. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2648691&tool=pmcentrez&rendertype=abstract
Kazama H, Ricci J-E, Herndon JM, Hoppe G, Green DR, Ferguson TA (2008) Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein. Immunity 29(1):21–32. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2704496&tool=pmcentrez&rendertype=abstract
Kim MM, Clinger JD, Masayesva BG, Ha PK, Zahurak ML, Westra WH, Califano JA (2004) Mitochondrial DNA quantity increases with histopathologic grade in premalignant and malignant head and neck lesions. Clin Cancer Res 10(24):8512–8515. http://www.ncbi.nlm.nih.gov/pubmed/15623632
Kim J, 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(3):177–185. http://www.ncbi.nlm.nih.gov/pubmed/16517405
Kim J, Gao P, Liu Y-C, Semenza GL, Dang CV (2007) Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1. Mol Cell Biol 27(21):7381–7393. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2169056&tool=pmcentrez&rendertype=abstract
Kim Y-S, Yang C-T, Wang J, Wang L, Li Z-B, Chen X, Liu S (2008) Effects of targeting moiety, linker, bifunctional chelator, and molecular charge on biological properties of 64Cu-labeled triphenylphosphonium cations. J Med Chem 51(10):2971–2984. http://www.lhl.uab.edu:15002/pubmed/18419113
Klimova T, Chandel NS (2008) Mitochondrial complex III regulates hypoxic activation of HIF. Cell Death Differ 15(4):660–666. http://www.ncbi.nlm.nih.gov/pubmed/18219320
Klingenberg M (1970) Localization of the glycerol-phosphate dehydrogenase in the outer phase of the mitochondrial inner membrane. Eur J Biochem/FEBS 13(2):247–252. http://www.ncbi.nlm.nih.gov/pubmed/5439930
Knight JRP, Milner J (2012) SIRT1, metabolism and cancer. Curr Opin Oncol 24(1): 68–75. doi:10.1097/CCO.0b013e32834d813b. http://www.ncbi.nlm.nih.gov/pubmed/22080944
Ko YH, Pedersen PL, Geschwind JF (2001) Glucose catabolism in the rabbit VX2 tumor model for liver cancer: characterization and targeting hexokinase. Cancer Lett 173(1):83–91. http://www.ncbi.nlm.nih.gov/pubmed/11578813
Kondoh H, Lleonart ME, Gil J, Wang J, Degan P, Peters G, Martinez D, Carnero A, Beach D (2005) Glycolytic enzymes can modulate cellular life span. Cancer Res 65(1):177–185. http://www.ncbi.nlm.nih.gov/pubmed/15665293
Koppenol WH, Bounds PL, Dang CV (2011) Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer 11(5):325–337. http://www.ncbi.nlm.nih.gov/pubmed/21508971
Kovacevic Z, McGivan JD (1983) Mitochondrial metabolism of glutamine and glutamate and its physiological significance. Physiol Rev 63(2):547–605. http://www.ncbi.nlm.nih.gov/pubmed/6132422
Kuhajda FP (2000) Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology. Nutrition 16(3):202–208. http://www.ncbi.nlm.nih.gov/pubmed/10705076
Küppers M, Ittrich C, Faust D, Dietrich C (2010) The transcriptional programme of contact-inhibition. J Cell Biochem 110(5):1234–1243. http://www.ncbi.nlm.nih.gov/pubmed/20564218
Kwak C, Jin RJ, Lee C, Park MS, Lee SE (2002) Thrombospondin-1, vascular endothelial growth factor expression and their relationship with P53 status in prostate cancer and benign prostatic hyperplasia. BJU International 89(3):303–309. http://www.ncbi.nlm.nih.gov/pubmed/11856116
Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N et al (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1. Cell 127(6):1109–1122. doi:10.1016/j.cell.2006.11.013. http://linkinghub.elsevier.com/retrieve/pii/S0092867406014280
Lampidis TJ, Bernal SD, Summerhayes IC, Chen LB (1983) Selective toxicity of rhodamine 123 in carcinoma cells in vitro. Cancer Res 43(2):716–720. http://www.ncbi.nlm.nih.gov/pubmed/6848187
Law AKT, Gupta D, Levy S, Wallace DC, McKeon RJ, Buck CR (2004) TGF-β1 induction of the adenine nucleotide translocator 1 in astrocytes occurs through Smads and Sp1 transcription factors. BMC Neuroscience 5:1. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=324399&tool=pmcentrez&rendertype=abstract
Le SB, Katie Hailer M, Buhrow S, Wang Q, Flatten K, Pediaditakis P, Bible KC et al (2007) Inhibition of mitochondrial respiration as a source of adaphostin-induced reactive oxygen species and cytotoxicity. J Biol Chem 282(12):8860–8872. http://www.jbc.org/content/282/12/8860.long
Lee H-C, Wei Y-H (2009) Mitochondrial DNA instability and metabolic shift in human cancers. Int J Mol Sci 10(2):674–701. http://www.ncbi.nlm.nih.gov/pubmed/19333428
Lee M, Hyun DH, Marshall KA, Ellerby LM, Bredesen DE, Jenner P, Halliwell B (2001) Effect of overexpression of Bcl-2 on cellular oxidative damage, nitric oxide production, antioxidant defenses, and the proteasome. Free Radic Biol Med 31(12):1550–1559. http://www.ncbi.nlm.nih.gov/pubmed/11744329
Lee H-C, Chang C-M, Chi C-W (2010) Somatic mutations of mitochondrial dna in aging and cancer progression. Ageing Res Rev 9(Suppl 1): S47–S58. http://www.ncbi.nlm.nih.gov/pubmed/20816876
Lee SY, Jeon HM, Ju MK, Kim CH, Yoon G, Han SI, Park HG, Kang HS (2012) Wnt/Snail signaling regulates cytochrome c oxidase and glucose metabolism. Cancer Res 2:3607–3617. doi:10.1158/0008–5472.CAN-12–0006. http://www.ncbi.nlm.nih.gov/pubmed/22637725
Lemarie A, Grimm S (2009) Mutations in the heme B-binding residue of SDHC inhibit assembly of respiratory chain complex II in mammalian cells. Mitochondrion 9(4):254–260. http://www.ncbi.nlm.nih.gov/pubmed/19332149
Lemarie A, Huc L, Pazarentzos E, Mahul-Mellier A-L, Grimm S (2011) Specific disintegration of complex II succinate: ubiquinone oxidoreductase links pH changes to oxidative stress for apoptosis induction. Cell Death Differ 18(2):338–349. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3044456&tool=pmcentrez&rendertype=abstract
Leverve XM, Guigas B, Detaille D, Batandier C, Koceir EA, Chauvin C, Fontaine E, Wiernsperger NF (2003) Mitochondrial metabolism and type-2 diabetes: a specific target of metformin. Diabetes Metab 29(4 Pt 2):6S88–S94. http://www.ncbi.nlm.nih.gov/pubmed/14502105
Li R, Hodny Z, Luciakova K, Barath P, Nelson BD (1996) Sp1 activates and inhibits transcription from separate elements in the proximal promoter of the human adenine nucleotide translocase 2 (ANT2) gene. J Biol Chem 271(31):18925–18930. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed & dopt=Citation&list_uids=8702555
Lluis JM, Buricchi F, Chiarugi P, Morales A, Fernandez-Checa JC (2007) Dual role of mitochondrial reactive oxygen species in hypoxia signaling: activation of nuclear factor-kappaB via c-SRC and oxidant-dependent cell death. Cancer Res 67(15):7368–7377. http://www.ncbi.nlm.nih.gov/pubmed/17671207
Locasale JW, Grassian AR, Melman T, Lyssiotis CA, Mattaini KR, Bass AJ, Heffron G et al (2011) Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat Genet 43(9):869–874. doi:10.1038/ng.890. http://www.ncbi.nlm.nih.gov/pubmed/21804546
López-Ríos F, Sánchez-Aragó M, García-García E, Ortega AD, Berrendero JR, Pozo-Rodríguez F, López-Encuentra A, Ballestín C, Cuezva JM (2007) Loss of the mitochondrial bioenergetic capacity underlies the glucose avidity of carcinomas. Cancer Res 67(19):9013–9017. http://www.ncbi.nlm.nih.gov/pubmed/17909002
Lu J, Sharma LK, Bai Y (2009) Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis. Cell Res 19(7):802–815. http://www.ncbi.nlm.nih.gov/pubmed/19532122
Luo W, Hu H, Chang R, Zhong J, Knabel M, O’Meally R, Cole RN, Pandey A, Semenza GL (2011) Pyruvate kinase M2 Is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 145(5):732–744. http://www.ncbi.nlm.nih.gov/pubmed/21620138
Lv L, Li D, Zhao D, Lin R, Chu Y, Zhang H, Zha Z et al (2011) Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth. Molecular Cell 42(6):719–730. http://www.ncbi.nlm.nih.gov/pubmed/21700219
Ma J-T, Han C-B, Zhou Y, Zhao J-Z, Jing W, Zou H-W (2012) Altered expression of mitochondrial cytochrome c oxidase I and NADH dehydrogenase 4 transcripts associated with gastric tumorigenesis and tumor dedifferentiation. Mol Med Rep 5(6):1526–1530. doi:10.3892/mmr.2012.832. http://www.ncbi.nlm.nih.gov/pubmed/22407105
Maas MFPM, Sellem CH, Krause F, Dencher NA, Sainsard-Chanet A (2010) Molecular gene therapy: overexpression of the alternative NADH dehydrogenase NDI1 restores overall physiology in a fungal model of respiratory complex I deficiency. J Mol Biol 399(1):31–40. http://www.ncbi.nlm.nih.gov/pubmed/20398675
Maher JC, Krishan A, Lampidis TJ (2004) Greater cell cycle inhibition and cytotoxicity induced by 2-deoxy-D-glucose in tumor cells treated under hypoxic vs aerobic conditions. Cancer Chemother Pharmacol 53(2):116–122. http://www.ncbi.nlm.nih.gov/pubmed/14605866
Marchetti P, Zamzami N, Joseph B, Schraen-Maschke S, Méreau-Richard C, Costantini P, Métivier D, Susin SA, Kroemer G, Formstecher P (1999) The novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphtalene carboxylic acid can trigger apoptosis through a mitochondrial pathway independent of the nucleus. Cancer Res 59(24):6257–6266. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10626821
Masgras I, Rasola A, Bernardi P (2012) Induction of the permeability transition pore in cells depleted of mitochondrial DNA. Biochim Biophys Acta 1817(10):2–8. doi:10.1016/j.bbabio.2012.02.022. http://www.ncbi.nlm.nih.gov/pubmed/22402226
Mashima T, Seimiya H, Tsuruo T (2009) De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy. Br J Cancer100(9):1369–1372. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2694429&tool=pmcentrez&rendertype=abstract
McCormack JG, Denton RM (1979) The effects of calcium ions and adenine nucleotides on the activity of pig heart 2-oxoglutarate dehydrogenase complex. Biochem J 180(3):533–544. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1161091&tool=pmcentrez&rendertype=abstract
Michelakis ED, Sutendra G, Dromparis P, Webster L, Haromy A, Niven E, Maguire C et al (2010) Metabolic modulation of glioblastoma with dichloroacetate. 2(31):31ra34. doi:10.1126/scitranslmed.3000677
Mihaylova MM, Shaw RJ (2011) The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat Cell Biol 13(9):1016–1023. doi:10.1038/ncb2329. http://www.nature.com/doifinder/10.1038/ncb2329
Minocherhomji S, Tollefsbol TO, Singh KK (2012) Mitochondrial regulation of epigenetics and its role in human diseases. Epigenetics 7(4):326–334. doi:10.4161/epi.19547. http://www.ncbi.nlm.nih.gov/pubmed/22419065
Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191(4784):144–148. doi:10.1038/191144a0. http://www.ncbi.nlm.nih.gov/pubmed/13771349
Mitchell P, Moyle J (1967) Respiration-driven proton translocation in rat liver mitochondria. Biochem J 105(3):1147–1162. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16742541
Modica-Napolitano JS, Aprille JR (1987) Basis for the selective cytotoxicity of rhodamine 123. Cancer Res 47(16):4361–4365. http://www.ncbi.nlm.nih.gov/pubmed/2886218
Modica-Napolitano JS, Aprille JR (2001) Delocalized lipophilic cations selectively target the mitochondria of carcinoma cells. Adv Drug Deliv Rev 49(1–2):63–70. http://www.ncbi.nlm.nih.gov/pubmed/11377803
Modica-napolitano JS, Kulawiec M, Singh KK (2007) Mitochondria and human cancer. Curr Mol Med 7(1):121–131
Moncada S, Erusalimsky JD (2002) Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nat Rev Mol Cell Biol 3(3):214–220. http://www.ncbi.nlm.nih.gov/pubmed/11994742
Moreadith RW, Lehninger AL (1984) The pathways of glutamate and glutamine oxidation by tumor cell mitochondria. Role of mitochondrial NAD(P)+ -dependent malic enzyme. J Biol Chem 259(10):6215–6221. http://www.ncbi.nlm.nih.gov/pubmed/6144677
Moreira PI, Custódio J, Moreno A, Oliveira CR, Santos MS (2006) Tamoxifen and estradiol interact with the flavin mononucleotide site of complex I leading to mitochondrial failure. J Biol Chem 281(15):10143–10152. http://www.ncbi.nlm.nih.gov/pubmed/16410252
Moreno-Sánchez R, Rodríguez-Enríquez S, Marín-Hernández A, Saavedra E (2007) Energy metabolism in tumor cells. FEBS J 274(6):1393–1418. http://www.ncbi.nlm.nih.gov/pubmed/17302740
Morfouace M, Lalier L, Bahut M, Bonamain V, Naveilhan P, Guette C, Oliver L, Gueguen N, Reynier P, Vallette FM (2012) Comparison of spheroids formed by rat glioma stem cells and neural stem cells reveals differences in glucose metabolism and promising therapeutic applications. J Biol Chem. doi:10.1074/jbc.M111.320028. http://www.ncbi.nlm.nih.gov/pubmed/22782899
Muñoz-Pinedo C, El Mjiyad N, Ricci JE (2012) Cancer metabolism: current perspectives and future directions. Cell Death Dis 3:e248. doi:10.1038/cddis.2011.123. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3270265&tool=pmcentrez&rendertype=abstract
Notario B, Zamora M, Viñas O, Mampel T (2003) All-trans-retinoic acid binds to and inhibits adenine nucleotide translocase and induces mitochondrial permeability transition. Mol Pharmacol 63(1):224–231. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12488555
Okamaoto M, Ohsato T, Nakada K, Isobe K, Spelbrink JN, Hayashi J-I, Hamasaki N, Kang D (2003) Ditercalinium chloride, a pro-anticancer drug, intimately associates with mammalian mitochondrial dna and inhibits its replication. Curr Genet 43(5):364–370. http://www.ncbi.nlm.nih.gov/pubmed/12679881
Ottino P, Duncan JR (1997) Effect of alpha-tocopherol succinate on free radical and lipid peroxidation levels in BL6 melanoma cells. Free Radic Biol Med 22(7):1145–1151. http://www.ncbi.nlm.nih.gov/pubmed/9098087
Ouaïssi M, Sielezneff I, Silvestre R, Sastre B, Bernard J-P, Lafontaine JP, Payan MJ et al (2008) High histone deacetylase 7 (HDAC7) expression is significantly associated with adenocarcinomas of the pancreas. Ann Surg Oncol 15(8):2318–2328. http://www.ncbi.nlm.nih.gov/pubmed/18506539
Owens KM, Kulawiec M, Desouki MM, Vanniarajan A, Singh KK (2011) Impaired OXPHOS complex III in breast cancer. PLoS ONE 6(8):10. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3162009&tool=pmcentrez&rendertype=abstract
Pani G, Koch OR, Galeotti T (2009) The p53-p66shc-manganese superoxide dismutase (MnSOD) network: a mitochondrial intrigue to generate reactive oxygen species. Int J Biochem Cell Biol 41(5):1002–1005. doi:10.1016/j.biocel.2008.10.011. http://www.ncbi.nlm.nih.gov/pubmed/18992840
Pani G, Galeotti T, Chiarugi P (2010) Metastasis: cancer cell’s escape from oxidative stress. Cancer Metastasis Rev 29(2):351–378. http://www.ncbi.nlm.nih.gov/pubmed/20386957
Papa S, De Rasmo D, Technikova-Dobrova Z, Panelli D, Signorile A, Scacco S, Petruzzella V et al (2011) Respiratory chain complex I, a main regulatory target of the cAMP/PKA pathway is defective in different human diseases. FEBS Lett 586(5):568–576. doi:10.1016/j.febslet.2011.09.019. http://www.ncbi.nlm.nih.gov/pubmed/21945319
Park JS, Sharma LK, Li H, Xiang R, Holstein D, Wu J, Lechleiter 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(9):1578–1589. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2733816&tool=pmcentrez&rendertype=abstract
Parlo RA, Coleman PS (1984) Enhanced rate of citrate export from cholesterol-rich hepatoma mitochondria. The truncated Krebs Cycle and other metabolic ramifications of mitochondrial membrane cholesterol. J Biol Chem 259(16):9997–10003. http://www.ncbi.nlm.nih.gov/pubmed/6469976
Pedersen PL (2007) The cancer cell’s ‘power plants’ as promising therapeutic targets: an overview. J Bioenerg Biomembr 39(1):1–12. doi:10.1007/s10863–007-9070–5. http://www.ncbi.nlm.nih.gov/pubmed/17404823
Pereira GC, Branco AF, Matos JAC, Pereira SL, Parke D, Perkins EL, Serafim TL et al (2007) Mitochondrially targeted effects of berberine [natural yellow 18, 5,6-dihydro-9,10-dimethoxybenzo(g)-1,3-benzodioxolo(5,6-a) quinolizinium] on K1735-M2 mouse melanoma cells: comparison with direct effects on isolated mitochondrial fractions. J Pharmacol Exp Ther 323(2):636–649. http://www.ncbi.nlm.nih.gov/pubmed/17704354
Pereira CV, Machado NG, Oliveira PJ (2008) Mechanisms of berberine (natural Yellow 18)-induced mitochondrial dysfunction: interaction with the adenine nucleotide translocator. Toxicol Sci 105(2):408–417. http://www.ncbi.nlm.nih.gov/pubmed/18599498
Petros JA, Baumann AK, Ruiz-Pesini E, Amin MB, Sun CQ, Hall J, Lim S et al (2005) mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci U S A 102(3):719–724. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=545582&tool=pmcentrez&rendertype=abstract
Pistollato F, Abbadi S, Rampazzo E, Persano L, Puppa AD, Frasson C, Sarto E, Scienza R, D’avella D, Basso G (2010) Intratumoral hypoxic gradient drives stem cells distribution and MGMT expression in glioblastoma. Stem Cells 28(5):851–862. http://www.ncbi.nlm.nih.gov/pubmed/20309962
Plescia J, Salz W, Xia F, Pennati M, Zaffaroni N, Daidone MG, Meli M et al (2005) Rational design of shepherdin, a novel anticancer agent. Cancer Cell 7(5):457–468. http://www.ncbi.nlm.nih.gov/pubmed/15894266
Pollak M (2012) The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer 12(3):159–169. doi:10.1038/nrc3215. http://www.ncbi.nlm.nih.gov/pubmed/22337149
Polyak K, Haviv I, Campbell IG (2009) Co-evolution of tumor cells and their microenvironment. Trends Genet 25(1):30–38. http://www.ncbi.nlm.nih.gov/pubmed/19054589
Porstmann T, Griffiths B, Chung Y-L, Delpuech O, Griffiths JR, Downward J, Schulze A (2005) PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP. Oncogene 24(43):6465–6481. http://www.ncbi.nlm.nih.gov/pubmed/16007182
Porstmann T, Santos CR, Lewis C, Griffiths B, Schulze A (2009) A new player in the orchestra of cell growth: SREBP activity is regulated by mTORC1 and contributes to the regulation of cell and organ size. Biochem Soc Trans 37(Pt 1):278–283. http://www.ncbi.nlm.nih.gov/pubmed/19143646
Possemato R, Marks KM, Shaul YD, Pacold ME, Kim D, Birsoy K, Sethumadhavan S et al (2011) Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 476(7360):346–350. doi:10.1038/nature10350. http://www.nature.com/doifinder/10.1038/nature10350
Prasad KN, Edwards-Prasad J (1982) Effects of tocopherol (vitamin E) acid succinate on morphological alterations and growth inhibition in melanoma cells in culture. Cancer Res 42(2):550–555. doi:0008–5472/82/0042-OOOOS02.00. http://www.ncbi.nlm.nih.gov/pubmed/6275980
Preuss M, Girnun GD, Darby CJ, Khoo N, Spector AA, Robbins ME (2000) Role of antioxidant enzyme expression in the selective cytotoxic response of glioma cells to gamma-linolenic acid supplementation. Free Radic Biol Med 28(7):1143–1156. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10832077
Putignani L, Raffa S, Pescosolido R, Aimati L, Signore F, Torrisi MR, Grammatico P (2008) Alteration of expression levels of the oxidative phosphorylation system (OXPHOS) in breast cancer cell mitochondria. Breast Cancer Res Treat 110(3):439–452. http://www.ncbi.nlm.nih.gov/pubmed/17899367
Raimundo N, Baysal BE, Shadel GS (2011) Revisiting the TCA cycle: signaling to tumor formation. Trends Mol Med 17(11):641–649. doi:10.1016/j.molmed.2011.06.001. http://www.ncbi.nlm.nih.gov/pubmed/21764377
Ralph SJ, Rodríguez-Enríquez S, Neuzil J, Moreno-Sánchez R (2010) bioenergetic pathways in tumor mitochondria as targets for cancer therapy and the importance of the ROS-induced apoptotic trigger. Mol Aspects Med 31(1):29–59. http://www.ncbi.nlm.nih.gov/pubmed/20026172
Ramanathan A, Wang C, Schreiber SL (2005) Perturbational profiling of a cell-line model of tumorigenesis by using metabolic measurements. Proc Natl Acad Sci U S A 102(17):5992–5997. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1087961&tool=pmcentrez&rendertype=abstract
Ramjaun AR, Downward J (2007) Ras and phosphoinositide 3-kinase: partners in development and tumorigenesis. Cell Cycle Georgetown Tex 6(23):2902–2905. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17993782
Ren J, Xiao Y, Singh LS, Zhao X, Zhao Z, Feng L, Rose TM, Prestwich GD, Xu Y (2006) Lysophosphatidic acid is constitutively produced by human peritoneal mesothelial cells and enhances adhesion, migration, and invasion of ovarian cancer cells. Cancer Res 66(6):3006–3014. http://www.ncbi.nlm.nih.gov/pubmed/16540649
Rikka S, Quinsay MN, Thomas RL, Kubli DA, Zhang X, Murphy AN, Gustafsson ÅB (2011) Bnip3 impairs mitochondrial bioenergetics and stimulates mitochondrial turnover. Cell Death Differ 18(4):721–731. http://www.ncbi.nlm.nih.gov/pubmed/21278801
Robey RB, Hay N (2006) Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene 25(34):4683–4696. http://www.ncbi.nlm.nih.gov/pubmed/16892082
Rodríguez-Enríquez S, Gallardo-Pérez JC, Avilés-Salas A, Marín-Hernández A, Carreño-Fuentes L, Maldonado-Lagunas V, Moreno-Sánchez R (2008) Energy metabolism transition in multi-cellular human tumor spheroids. J Cell Physiol 216(1):189–197. http://www.ncbi.nlm.nih.gov/pubmed/18264981
Rossier MF. (2006) T channels and steroid biosynthesis: in search of a link with mitochondria. Cell Calcium 40(2):155–164. http://www.ncbi.nlm.nih.gov/pubmed/16759697
Rossignol R, Gilkerson R, Aggeler R, Yamagata K, Remington SJ, Capaldi RA (2004) Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells. Cancer Res 64(3):985–993. doi:10.1158/0008–5472.CAN-03–1101. http://cancerres.aacrjournals.org/cgi/doi/10.1158/0008–5472.CAN-03–1101
Ruan K, Song G, Ouyang G (2009) Role of hypoxia in the hallmarks of human cancer. J Cell Biochem 107(6):1053–1062. http://www.ncbi.nlm.nih.gov/pubmed/19479945
Samoszuk MK, Walter J, Mechetner E (2004) Improved immunohistochemical method for detecting hypoxia gradients in mouse tissues and tumors. J Histochem Cytochem 52(6):837–839. http://jhc.sagepub.com/lookup/doi/10.1369/jhc.4B6248.2004
Sánchez-Cenizo L, Formentini L, Aldea M, Ortega ÁlvaroD, García-Huerta P, Sánchez-Aragó M, Cuezva JM (2010) Up-regulation of the ATPase inhibitory factor 1 (IF1) of the mitochondrial H+ -ATP synthase in human tumors mediates the metabolic shift of cancer cells to a Warburg phenotype. J Biol Chem 285(33):25308–25313.http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2919093&tool=pmcentrez&rendertype=abstract
Santandreu FM, Valle A, De SF, Roca P, Oliver J (2009) Cellular physiology biochemistry and biochemistry hydrogen peroxide regulates the mitochondrial content of uncoupling protein 5 in colon cancer cells. Cell Physiol Biochem 24:379–390
Sasaki R, Suzuki Y, Yonezawa Y, Ota Y, Okamoto Y, Demizu Y, Huang P, Yoshida H, Sugimura K, Mizushina Y (2008) DNA polymerase gamma inhibition by vitamin K3 induces mitochondria-mediated cytotoxicity in human cancer cells. Cancer Sci 99(5):1040–1048. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18312466
Schwartzenberg-Bar-Yoseph F, Armoni M, Karnieli E (2004) The tumor suppressor P53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res 64(7):2627–2633. http://cancerres.aacrjournals.org/cgi/doi/10.1158/00085472.CAN-030846
Segal-Bendirdjian E, Coulaud D, Roques BP, Le Pecq JB (1988) Selective loss of mitochondrial DNA after treatment of cells with ditercalinium (NSC 335153), an antitumor bis-intercalating agent. Cancer Res 48(17):4982–4992
Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD, Pan Y, Simon MC, Thompson CB, Gottlieb E (2005) Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase. Cancer Cell 7: 77–85. http://dx.doi.org/10.1016/j.ccr.2004.11.022
Semenza GL (2007) HIF-1 mediates the Warburg effect in clear cell renal carcinoma. J Bioenerg Biomembr 39(3):231–234. http://www.ncbi.nlm.nih.gov/pubmed/17551816
Sen N, Satija YK, Das S (2011) PGC-1α, a key modulator of P53, promotes cell survival upon metabolic stress. Molecular Cell 44(4):621–634. doi:10.1016/j.molcel.2011.08.044. http://linkinghub.elsevier.com/retrieve/pii/S1097276511008173
Serafim TL, Matos JAC, Sardão VA, Pereira GC, Branco AF, Pereira SL, Parke D et al (2008) Sanguinarine cytotoxicity on mouse melanoma K1735-M2 cells–nuclear vs. mitochondrial effects. Biochem Pharmacol 76(11):1459–1475. http://www.ncbi.nlm.nih.gov/pubmed/18692024.
Serafim TL, Oliveira PJ, Sardao VA, Perkins E, Parke D, Holy J (2008) Different concentrations of berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line. Cancer Chemother Pharmacol 61(6):1007–1018. http://www.ncbi.nlm.nih.gov/pubmed/17661039
Sermeus A, Michiels C (2011) Reciprocal influence of the P53 and the hypoxic pathways. Cell Death Dis 2(5):e164. http://www.nature.com/doifinder/10.1038/cddis.2011.48
Sheng H, Niu B, Sun H (2009) Metabolic targeting of cancers: from molecular mechanisms to therapeutic strategies. Curr Med Chem 16(13):1561–1587. http://www.ncbi.nlm.nih.gov/pubmed/19442134
Shidara Y, Yamagata K, Kanamori T, Nakano K, Kwong JQ, Manfredi G, Oda H, Ohta S (2005) Positive contribution of pathogenic mutations in the mitochondrial genome to the promotion of cancer by prevention from apoptosis. Cancer Res 65(5):1655–1663. http://www.ncbi.nlm.nih.gov/pubmed/15753359
Shulga N, Wilson-Smith R, Pastorino JG (2010) Sirtuin-3 deacetylation of cyclophilin D induces dissociation of hexokinase II from the mitochondria. J Cell Sci 123(Pt 6):894–902. http://www.ncbi.nlm.nih.gov/pubmed/20159966
Siegelin MD, Plescia J, Raskett CM, Gilbert CA, Ross AH, Altieri DC (2010) Global targeting of subcellular heat shock protein-90 networks for therapy of glioblastoma. Mol Cancer Ther 9(6):1638–1646. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2884083&tool=pmcentrez&rendertype=abstract
Simonnet H, Alazard N, Pfeiffer K, Gallou C, Béroud C, Demont J, Bouvier R, Schägger H, Godinot C (2002) Low mitochondrial respiratory chain content correlates with tumor aggressiveness in renal cell carcinoma. Carcinogenesis 23(5):759–768. http://www.ncbi.nlm.nih.gov/pubmed/12016148
Skala MC, Fontanella A, Lan L, Izatt JA, Dewhirst MW (2010) Longitudinal optical imaging of tumor metabolism and hemodynamics. J Biomed Opt 15(1):011112. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2816992&tool=pmcentrez&rendertype=abstract
Slane BG, Aykin-Burns N, Smith BJ, Kalen AL, Goswami PC, Domann FE, Spitz DR (2006) Mutation of succinate dehydrogenase subunit C results in increased O2.-, oxidative stress, and genomic instability. Cancer Res 66(15):7615–7620. doi:10.1158/0008–5472.CAN-06–0833. http://www.ncbi.nlm.nih.gov/pubmed/16885361
Sokolosky ML, Wargovich MJ (2012) Homeostatic imbalance and colon cancer: the dynamic epigenetic interplay of inflammation, environmental toxins, and chemopreventive plant compounds. Front Oncol 2:57. doi:10.3389/fonc.2012.00057. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3365481&tool=pmcentrez&rendertype=abstract
Solaini G, Sgarbi G, Baracca A (2011) Oxidative phosphorylation in cancer cells. Biochim Biophys Acta 1807(6):534–542. http://www.ncbi.nlm.nih.gov/pubmed/20849810
St-Pierre J, Brand MD, Boutilier RG (2000) Mitochondria as ATP consumers: cellular treason in anoxia. Proc Natl Acad Sci U S A 97(15):8670–8674. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=27006&tool=pmcentrez&rendertype=abstract
Stockwin LH, Yu SX, Borgel S, Hancock C, Wolfe TL, Phillips LR, Hollingshead MG, Newton DL (2010) Sodium dichloroacetate selectively targets cells with defects in the mitochondrial ETC. Int J Cancer 127(11):2510–2519. doi:10.1002/ijc.25499. http://www.ncbi.nlm.nih.gov/pubmed/20533281
Stubbs M, Rodrigues L, Howe FA, Wang J, Jeong K, Veech RL, Griffiths JI (1994) Metabolic consequences of a reversed pH gradient in rat tumors. Cancer Res 54:4011–4016
Stuelten CH, Barbul A, Busch JI, Sutton E, Katz R, Sato M, Wakefield LM, Roberts AB, Niederhuber JE (2008) Acute wounds accelerate tumorigenesis by a T cell-dependent mechanism. Cancer Res 68(18):7278–7282. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2766858&tool=pmcentrez&rendertype=abstract
Suhane S, Berel D, Ramanujan VK (2011) Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma. Biochem Biophys Res Commun 412(4):590–595
Sun AS, Cederbaum AI (1980) Oxidoreductase activities in normal rat liver, tumor-bearing rat liver, and hepatoma HC-252. Cancer Res 40(12):4677–4681
Swinnen JV, Brusselmans K, Verhoeven G (2006) Increased lipogenesis in cancer cells: new players, novel targets. Curr Opin Clin Nutr Metab Care 9(4):358–365. http://www.ncbi.nlm.nih.gov/pubmed/16778563
Taddei ML, Giannoni E, Raugei G, Scacco S, Sardanelli AM, Papa S, Chiarugi P (2012) Mitochondrial oxidative stress due to complex I dysfunction promotes fibroblast activation and melanoma cell invasiveness. J Signal Transduct 2012:684592. doi:10.1155/2012/684592. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3261495&tool=pmcentrez&rendertype=abstract
Tamada M, Nagano O, Tateyama S, Ohmura M, Yae T, Ishimoto T, Sugihara E et al (2012) Modulation of glucose metabolism by CD44 contributes to antioxidant status and drug resistance in cancer cells. Cancer Res 72(6):1438–1448. doi:10.1158/0008–5472.CAN-11–3024. http://www.ncbi.nlm.nih.gov/pubmed/22293754
Tan D-J, Bai R-K, Wong L-J (2002) Comprehensive scanning of somatic mitochondrial DNA mutations in breast cancer. Cancer Res 62(4):972–976. http://www.ncbi.nlm.nih.gov/pubmed/11861366
Tannock IF, Rotin D (1989) Acid pH in tumors and its potential for therapeutic exploitation. Cancer Res 49(16):4373–4384. http://www.ncbi.nlm.nih.gov/pubmed/2545340
Tao R, Coleman MC, Pennington JD, Ozden O, Park S-H, Jiang H, Kim H-S et al (2010) Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress. Mol Cell 40(6):893–904. http://www.ncbi.nlm.nih.gov/pubmed/21172655
Taubes G (2012) Cancer research. Cancer prevention with a diabetes pill? Science 335(6064):29. doi:10.1126/science.335.6064.29. http://www.ncbi.nlm.nih.gov/pubmed/22223788
Taylor CT (2008) Mitochondria and cellular oxygen sensing in the HIF pathway. Biochem J 409(1):19–26. http://www.ncbi.nlm.nih.gov/pubmed/18062771
Toullec A, Gerald D, Despouy G, Bourachot B, Cardon M, Lefort S, Richardson M et al (2010) Oxidative stress promotes myofibroblast differentiation and tumour spreading. EMBO Mol Med 2(6):211–230. http://www.ncbi.nlm.nih.gov/pubmed/20535745
Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8(7):579–591. http://www.ncbi.nlm.nih.gov/pubmed/19478820
Tsujio I, Tanaka T, Kudo T, Nishikawa T, Shinozaki K, Grundke-Iqbal I, Iqbal K, Takeda M (2000) Inactivation of glycogen synthase kinase-3 by protein kinase C delta: implications for regulation of tau phosphorylation. FEBS Lett 469(1):111–117. http://www.ncbi.nlm.nih.gov/pubmed/10708767
Vander H Matthew G, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324(5930):1029–1033. http://www.ncbi.nlm.nih.gov/pubmed/19460998
Vander H, Matthew G, Locasale JW, Swanson KD, Sharfi H, Heffron GJ, Amador-Noguez D, Christofk HR et al (2010) Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 329(5998):1492–1499. doi:10.1126/science.1188015. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3030121&tool=pmcentrez&rendertype=abstract
Van De Parre TJ, Martinet W, Verheye S, Kockx MM, Van Langenhove G, Herman AG, De Meyer GR (2008) Mitochondrial uncoupling protein 2 mediates temperature heterogeneity in atherosclerotic plaques. Cardiovasc Res 77(2):425–431. http://www.ncbi.nlm.nih.gov/pubmed/18006489
Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 49(23):6449–6465. http://www.ncbi.nlm.nih.gov/pubmed/2684393
Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, Guarente L, Weinberg RA (2001) hSIR2(SIRT1) functions as an NAD-dependent P53 deacetylase. Cell 107(2):149–159. http://www.ncbi.nlm.nih.gov/pubmed/11672523
Votyakova TV, Reynolds IJ (2001) DeltaPsi(m)-dependent and -independent production of reactive oxygen species by rat brain mitochondria. J Neurochem79(2):266–277. http://www.ncbi.nlm.nih.gov/pubmed/11677254
Walle T, Hsieh F, DeLegge MH, Oatis JE, Walle UK. (2004) High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos 32(12):1377–1382. http://www.ncbi.nlm.nih.gov/pubmed/15333514
Wang R, Dillon CP, Shi LZ, Milasta S, Carter R, Finkelstein D, McCormick LL et al (2011) The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity 35(6):871–882. doi:10.1016/j.immuni.2011.09.021. http://linkinghub.elsevier.com/retrieve/pii/S1074761311005152
Warburg O, Wind F, Negelein E (1927) The metabolism of tumors in the body. J Gen Physiol 8(6):519–530. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2140820&tool=pmcentrez&rendertype=abstract
Ward PS, Thompson CB (2012) Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell 21(3):297–308. doi:10.1016/j.ccr.2012.02.014. http://linkinghub.elsevier.com/retrieve/pii/S1535610812000785
Weinberg RA (2007) A multi-step model for the development of colorectal cancer. The biology of cancer. Garland Science, New York
Weisberg EL, Koya K, Modica-Napolitano J, Li Y, Chen LB (1996) In vivo administration of MKT-077 causes partial yet reversible impairment of mitochondrial function. Cancer Res 56(3):551–555
Weiss MJ, Wong JR, Ha CS, Bleday R, Salem RR, Steele GD, Chen LB (1987) Dequalinium, a topical antimicrobial agent, displays anticarcinoma activity based on selective mitochondrial accumulation. Proc Natl Acad Sci U S A 84(15):5444–5448. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=298874&tool=pmcentrez&rendertype=abstract
D’Souza Gerard GM, Weissig V (2010) Chapter I. An introduction to subcellular nanomedicine: current trends and future developments. Organelle‐specific pharmaceutical nanotechnology. Wiley.
Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB (2009) ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324(5930):1076–1080. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2746744&tool=pmcentrez&rendertype=abstract
Wenzel U, Nickel A, Daniel H (2005) Increased carnitine-dependent fatty acid uptake into mitochondria of human colon cancer cells induces apoptosis. J Nutr 135(6):1510–1514
Whitaker-Menezes D, Martinez-Outschoorn UE, Flomenberg N, Birbe RC, Witkiewicz AK, Howell A, Pavlides S et al (2011) Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells in situ: visualizing the therapeutic effects of metformin in tumor tissue. Cell Cycle Georgetown Tex 10(23):4047–4064. doi:10.4161/cc.10.23.18151. http://www.ncbi.nlm.nih.gov/pubmed/22134189
Wu C-H, Van Riggelen J, Yetil A, Fan AC, Bachireddy P, Felsher DW (2007) Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation. Proc Natl Acad Sci U S A 104(32):13028–13033. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1941831&tool=pmcentrez&rendertype=abstract
Yang Y-A, Han WF, Morin PJ, Chrest FJ, Pizer ES (2002) Activation of fatty acid synthesis during neoplastic transformation: role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Exp Cell Res 279(1):80–90. http://www.ncbi.nlm.nih.gov/pubmed/11716532
Yotnda P, Wu D, Swanson AM (2010) Hypoxic tumors and their effect on immune cells and cancer therapy. Methods Mol Biol 651:1–29. http://www.ncbi.nlm.nih.gov/pubmed/20686957
Yu W, Sanders BG, Kline K (2003) RRR-alpha-tocopheryl succinate-induced apoptosis of human breast cancer cells involves bax translocation to mitochondria. Cancer Res 63(10):2483–2491. http://www.ncbi.nlm.nih.gov/pubmed/12750270
Yu W, Dittenhafer-Reed KE, Denu JM (2012) SIRT3 deacetylates isocitrate dehydrogenase 2 (IDH2) and regulates mitochondrial redox status. J Biol Chem 2(17):14078–14086. doi:10.1074/jbc.M112.355206. http://www.ncbi.nlm.nih.gov/pubmed/22416140
Yuan TL, Cantley LC (2008) PI3K pathway alterations in cancer: variations on a theme. Oncogene 27(41):5497–5510. doi:10.1038/onc.2008.245. http://www.ncbi.nlm.nih.gov/pubmed/18794884
Yuneva M, Zamboni N, Oefner P, Sachidanandam R, Lazebnik Y (2007) Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells. J Cell Biol 178(1):93–105. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2064426&tool=pmcentrez&rendertype=abstract
Yusnita Y, Norsiah MD, Rahman AJ (2010) Mutations in mitochondrial NADH dehydrogenase subunit 1 (mtND1) gene in colorectal carcinoma. Malays J Pathol 32(2):103–110. http://www.ncbi.nlm.nih.gov/pubmed/21329181
Zhang T, Chen G, Wang Z, Wang Z, Chen S, Chen Z (2001) Arsenic trioxide, a therapeutic agent for APL. Oncogene 20:7146–7153
Zhang J, Frerman FE, Kim J-JP (2006) Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool. Proc Natl Acad Sci U S A 103(44):16212–16217. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1637562&tool=pmcentrez&rendertype=abstract
Zhang E, Zhang C, Su Y, Cheng T, Shi C (2011) Newly developed strategies for multifunctional mitochondria-targeted agents in cancer therapy. Drug Discov Today 16(3–4):140–146. http://www.ncbi.nlm.nih.gov/pubmed/21182981
Zhao Y, Coloff JL, Ferguson EC, Jacobs SR, Cui K, Rathmell JC (2008) Glucose metabolism attenuates P53 and puma-dependent cell death upon growth factor deprivation. J Biol Chem 283(52):36344–36353. doi:10.1074/jbc.M803580200. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2606014&tool=pmcentrez&rendertype=abstract
Zhuang D, Mannava S, Grachtchouk V, Tang W-H, Patil S, Wawrzyniak JA, Berman AE et al (2008) C-MYC overexpression is required for continuous suppression of oncogene-induced senescence in melanoma cells. Oncogene 27(52):6623–6634. http://www.ncbi.nlm.nih.gov/pubmed/18679422
Zimmermann FA, Mayr JA, Feichtinger R, Neureiter D, Lechner R, Koegler C, Ratschek M et al (2011) Respiratory chain complex I is a mitochondrial tumor suppressor of oncocytic tumors. BioScience 3(4):315–325. http://www.ncbi.nlm.nih.gov/pubmed/21196312
Zini R, Morin C, Bertelli A, Bertelli AA, Tillement JP (1999) Effects of resveratrol on the rat brain respiratory chain. Drugs Exp Clin Res 25(2–3):87–97. http://www.ncbi.nlm.nih.gov/pubmed/10370869
Zoncu R, Efeyan A, Sabatini DM (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12(1):21–35. http://www.ncbi.nlm.nih.gov/pubmed/21157483
Zu XL, Guppy M (2004) Cancer metabolism: facts, fantasy, and fiction. Biochem Biophys Res Commun 313(3):459–465. http://linkinghub.elsevier.com/retrieve/pii/S0006291X0302504X
Acknowledgments
We are very grateful to Alexandra Holy for English proofreading this manuscript. Research in the authors’ laboratory is funded by the Foundation for Science and Technology, Portugal (grants PTDC/QUI‐QUI/101409/2008, PTDC/QUIBIQ/101052/2008 and PEst‐C/SAU/LA0001/2013‐2014, co‐sponsored by FEDER/Compete and National funds).
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Serafim, T., Oliveira, P. (2014). Regulating Mitochondrial Respiration in Cancer. In: Kanner, S. (eds) Tumor Metabolome Targeting and Drug Development. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9545-1_3
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