Abstract
It has long been recognised that malignant tumours favour aerobic glycolysis to generate ATP and contain abnormalities of the intrinsic, mitochondria-dependent, apoptotic pathway, suggesting the involvement of dysfunctional mitochondria in tumour pathophysiology. However, the mechanisms underlying such processes in gliomas are poorly understood. Few recent studies have evaluated mitochondrial ultrastructure and proteomics in the pathophysiology of malignant gliomas. However, aberrant energy metabolism has been reported in gliomas and mitochondrial dysfunction links to glioma apoptotic signalling have been observed. Mitochondrial structural abnormalities and dysfunction in malignant gliomas is a neglected area of research. Definition of abnormalities in mitochondrial proteomics, membrane potential regulation, energy metabolism and intrinsic apoptotic pathway signalling in gliomas may open novel therapeutic opportunities.
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Legler JM, Ries LA, Smith MA, Warren JL, Heineman EF, Kaplan RS, Linet MS (1999) Cancer surveillance series: brain and other central nervous system cancers: recent trends in incidence and mortality. J Natl Cancer Inst 91:1382–1390
Wrensch M, Minn Y, Chew T, Bondy M, Berger MS (2002) Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro Oncol 4:278–299
DeAngelis LM (2001) Brain tumors. N Engl J Med 344:114–123
Radhakrishnan K, Mokri B, Parisi JE, O’Fallon WM, Sunku J, Kurland LT (1995) The trends in incidence of primary brain tumors in the population of Rochester, Minnesota. Ann Neurol 37:67–73
Landis SH, Murray T, Bolden S, Wingo PA (1999) Cancer statistics. CA Cancer J Clin 49:8–31
Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, Chin L, DePinho RA, Cavenee WK (2007) Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev 21:2683–2710
Larjavaara S, Mäntylä R, Salminen T, Haapasalo H, Raitanen J, Jääskeläinen J, Auvinen A (2007) Incidence of gliomas by anatomic location. Neuro Oncol 9:319–325
Inskip PD, Linet MS, Heineman EF (1995) Etiology of brain tumors in adults. Epidemiol Rev 17:382–414
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2007) WHO classification of tumours of the central nervous system, 4th edn. IARC, Lyon
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109
Rich JN, Bigner DD (2004) Development of novel targeted therapies in the treatment of malignant glioma. Nat Rev Drug Discov 3:430–446
Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, Burkhard C, Schüler D, Probst-Hensch NM, Maiorka PC, Baeza N, Pisani P, Yonekawa Y, Yasargil MG, Lütolf UM, Kleihues P (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64:6892–6899
Anderson E, Grant R, Lewis SC, Whittle IR (2004) Randomized phase III controlled trials of therapy in malignant glioma: where are we after 40 years? Br J Neurosurg (2008) 22:339–349
Glioma Meta-Analysis Trialists (GMT) Group (2002) Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet 359:1011–1018
Ziegler DS, Kung AL, Kieran MW (2008) Anti-apoptosis mechanisms in malignant gliomas. J Clin Oncol 26:493–500
Seyfried TN, Mukherjee P (2005) Targeting energy metabolism in brain cancer: review and hypothesis. Nutr Metab 2:30
Benard G, Rossignol R (2008) Ultrastructure of the mitochondrion and its bearing on function and bioenergetics. Antioxid Redox Signal 10:1313–1342
Nicholls DG, Budd SL (2000) Mitochondria and neuronal survival. Physiol Rev 80:315–360
Hertz L, Peng L, Dienel GA (2007) Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J Cereb Blood Flow Metab 27:219–249
Owen OE, Morgan AP, Kemp HG, Sullivan JM, Herrera MG, Cahill GF Jr (1967) Brain metabolism during fasting. J Clin Invest 46:1589–1595
Pellerin L, Bergersen LH, Halestrap AP, Pierre K (2005) Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain. J Neurosci Res 79:55–64
Froberg MK, Gerhart DZ, Enerson BE, Manivel C, Guzman-Paz M, Seacotte N, Drewes LR (2001) Expression of monocarboxylate transporter MCT1 in normal and neoplastic human CNS tissues. Neuroreport 12:761–765
Cahill GF Jr (2006) Fuel metabolism in starvation. Annu Rev Nutr 26:1–22
Veech RL, Chance B, Kashiwaya Y, Lardy HA, Cahill GF Jr (2001) Ketone bodies, potential therapeutic uses. IUBMB Life 51:241–247
Seyfried TN, Sanderson TM, El-Abbadi MM, McGowan R, Mukherjee P (2003) Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. Br J Cancer 89:1375–1382
Galarraga J, Loreck DJ, Graham JF, DeLaPaz RL, Smith BH, Hallgren D, Cummins CJ (1986) Glucose metabolism in human gliomas: correspondence of in situ and in vitro metabolic rates and altered energy metabolism. Metab Brain Dis 1:279–291
Roslin M, Henriksson R, Bergström P, Ungerstedt U, Bergenheim AT (2003) Baseline levels of glucose metabolites, glutamate and glycerol in malignant glioma assessed by stereotactic microdialysis. J Neurooncol 61:151–160
Williams ZR, Goodman CB, Soliman KF (2007) Anaerobic glycolysis protection against 1-methy-4-phenylpyridinium (MPP+) toxicity in C6 glioma cells. Neurochem Res 32:1071–1080
Warburg O (ed) (1931) The metabolism of tumours. Richard R. Smith, New York
Roeder LM, Poduslo SE, Tildon JT (1982) Utilization of ketone bodies and glucose by established neural cell lines. J Neurosci Res 8:671–682
Patel MS, Russell JJ, Gershman H (1981) Ketone-body metabolism in glioma and neuroblastoma cells. Proc Natl Acad Sci U S A 78:7214–7218
Zhou W, Mukherjee P, Kiebish MA, Markis WT, Mantis JG, Seyfried TN (2007) The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutr Metab 4:5
Nebeling LC, Miraldi F, Shurin SB, Lerner E (1995) Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr 14:202–208
Mukherjee P, Abate LE, Seyfried TN (2004) Antiangiogenic and proapoptotic effects of dietary restriction on experimental mouse and human brain tumors. Clin Cancer Res 10:5622–5629
Mukherjee P, El-Abbadi MM, Kasperzyk JL, Ranes MK, Seyfried TN (2002) Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model. Br J Cancer 86:1615–1621
Andersson AK, Rönnbäck L, Hansson E (2005) Lactate induces tumour necrosis factor-alpha, interleukin-6 and interleukin-1beta release in microglial- and astroglial-enriched primary cultures. J Neurochem 93:1327–1333
Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR, Zhuang H, Cinalli RM, Alavi A, Rudin CM, Thompson CB (2004) Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 64:3892–3899
Schlame M, Rua D, Greenberg ML (2000) The biosynthesis and functional role of cardiolipin. Prog Lipid Res 39:257–288
Ardail D, Privat JP, Egret-Charlier M, Levrat C, Lerme F, Louisot P (1990) Mitochondrial contact sites. Lipid composition and dynamics. J Biol Chem 265:18797–18802
LeCcocq J, Ballou CE (1964) On the structure of cardiolipin. Biochemistry 3:976–980
Schlame M, Brody S, Hostetler KY (1993) Mitochondrial cardiolipin in diverse eukaryotes. Comparison of biosynthetic reactions and molecular acyl species. Eur J Biochem 212:727–735
Schlame M, Hostetler KY (1997) Cardiolipin synthase from mammalian mitochondria. Biochim Biophys Acta 1348:207–213
Fry M, Green DE (1981) Cardiolipin requirement for electron transfer in complex I and III of the mitochondrial respiratory chain. J Biol Chem 256:1874–1880
Robinson NC, Zborowski J, Talbert LH (1990) Cardiolipin-depleted bovine heart cytochrome c oxidase: binding stoichiometry and affinity for cardiolipin derivatives. Biochemistry 29:8962–8969
Robinson NC (1993) Functional binding of cardiolipin to cytochrome c oxidase. J Bioenerg Biomembr 25:153–163
Eble KS, Coleman WB, Hantgan RR, Cunningham CC (1990) Tightly associated cardiolipin in the bovine heart mitochondrial ATP synthase as analyzed by 31P nuclear magnetic resonance spectroscopy. J Biol Chem 265:19434–19440
Beyer K, Klingenberg M (1985) ADP/ATP carrier protein from beef heart mitochondria has high amounts of tightly bound cardiolipin, as revealed by 31P nuclear magnetic resonance. Biochemistry 24:3821–3826
Hoffmann B, Stöckl A, Schlame M, Beyer K, Klingenberg M (1994) The reconstituted ADP/ATP carrier activity has an absolute requirement for cardiolipin as shown in cysteine mutants. J Biol Chem 269:1940–1944
Bogdanov M, Mileykovskaya E, Dowhan W (2008) Lipids in the assembly of membrane proteins and organization of protein supercomplexes: implications for lipid-linked disorders. Subcell Biochem 49:197–239
Jiang F, Ryan MT, Schlame M, Zhao M, Gu Z, Klingenberg M, Pfanner N, Greenberg ML (2000) Absence of cardiolipin in the crd1 null mutant results in decreased mitochondrial membrane potential and reduced mitochondrial function. J Biol Chem 275:22387–22394
Kiebish MA, Han X, Cheng H, Chuang JH, Seyfried TN (2008) Brain mitochondrial lipid abnormalities in mice susceptible to spontaneous gliomas. Lipids 43:951–959
Kiebish MA, Han X, Cheng H, Chuang JH, Seyfried TN (2008) Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer. J Lipid Res 49:2545–2556
Poli G, Leonarduzzi G, Biasi F, Chiarpotto E (2004) Oxidative stress and cell signalling. Curr Med Chem 11:1163–1182
Lee HC, Wei YH (2005) Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress. Int J Biochem Cell Biol 37:822–834
Almeida A, Delgado-Esteban M, Bolaños JP, Medina JM (2002) Oxygen and glucose deprivation induces mitochondrial dysfunction and oxidative stress in neurones but not in astrocytes in primary culture. J Neurochem 81:207–217
Santandreu FM, Brell M, Gene AH, Guevara R, Oliver J, Couce ME, Roca P (2008) Differences in mitochondrial function and antioxidant systems between regions of human glioma. Cell Physiol Biochem 22:757–768
Jelluma N, Yang X, Stokoe D, Evan GI, Dansen TB, Haas-Kogan DA (2006) Glucose withdrawal induces oxidative stress followed by apoptosis in glioblastoma cells but not in normal human astrocytes. Mol Cancer Res 4:319–330
Petrosillo G, Ruggiero FM, Di Venosa N, Paradies G (2003) Decreased complex III activity in mitochondria isolated from rat heart subjected to ischemia and reperfusion: role of reactive oxygen species and cardiolipin. FASEB J 17:714–716
Petrosillo G, Di Venosa N, Ruggiero FM, Pistolese M, D’Agostino D, Tiravanti E, Fiore T, Paradies G (2005) Mitochondrial dysfunction associated with cardiac ischemia/reperfusion can be attenuated by oxygen tension control. Role of oxygen-free radicals and cardiolipin. Biochim Biophys Acta 1710:78–86
Petrosillo G, Portincasa P, Grattagliano I, Casanova G, Matera M, Ruggiero FM, Ferri D, Paradies G (2007) Mitochondrial dysfunction in rat with nonalcoholic fatty liver involvement of complex I, reactive oxygen species and cardiolipin. Biochim Biophys Acta 1767:1260–1267
Degterev A, Boyce M, Yuan J (2003) A decade of caspases. Oncogene 22:8543–8567
Klein S, McCormick F, Levitzki A (2005) Killing time for cancer cells. Nat Rev Cancer 5:573–580
Frank S, Köhler U, Schackert G, Schackert HK (1999) Expression of TRAIL and its receptors in human brain tumors. Biochem Biophys Res Commun 257:454–459
Kuijlen JM, Mooij JJ, Platteel I, Hoving EW, van der Graaf WT, Span MM, Hollema H, den Dunnen WF (2006) TRAIL-receptor expression is an independent prognostic factor for survival in patients with a primary glioblastoma multiforme. J Neurooncol 78:161–171
Hao C, Beguinot F, Condorelli G, Trencia A, Van Meir EG, Yong VW, Parney IF, Roa WH, Petruk KC (2001) Induction and intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apotosis in human malignant glioma cells. Cancer Res 61:1162–1170
Puduvalli VK, Sampath D, Bruner JM, Nangia J, Xu R, Kyritsis AP (2005) TRAIL-induced apoptosis in gliomas is enhanced by Akt-inhibition and is independent of JNK activation. Apoptosis 10:233–243
Panner A, James CD, Berger MS, Pieper RO (2005) mTOR controls FLIPS translation and TRAIL sensitivity in glioblastoma multiforme cells. Mol Cell Biol 25:8809–8823
O’Neill J, Manion M, Schwartz P, Hockenbery DM (2004) Promises and challenges of targeting Bcl-2 anti-apoptotic proteins for cancer therapy. Biochim Biophys Acta 1705:43–51
Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163
Zoratti M, Szabò I (1995) The mitochondrial permeability transition. Biochim Biophys Acta 1241:139–176
Reifenberger J, Ring GU, Gies U, Cobbers L, Oberstrass J, An HX, Niederacher D, Wechsler W, Reifenberger G (1996) Analysis of p53 mutation and epidermal growth factor receptor amplification in recurrent gliomas with malignant progression. J Neuropathol Exp Neurol 55:822–831
Gaiser T, Becker MR, Meyer J, Habel A, Siegelin MD (2009) p53-mediated inhibition of angiogenesis in diffuse low-grade astrocytomas. Neurochem Int 54:458–463
Weller M, Malipiero U, Aguzzi A, Reed JC, Fontana A (1995) Protooncogene bcl-2 gene transfer abrogates Fas/APO-1 antibody-mediated apoptosis of human malignant glioma cells and confers resistance to chemotherapeutic drugs and therapeutic irradiation. J Clin Invest 95:2633–2643
Krajewski S, Krajewska M, Ehrmann J, Sikorska M, Lach B, Chatten J, Reed JC (1997) Immunohistochemical analysis of Bcl-2, Bcl-X, Mcl-1, and Bax in tumors of central and peripheral nervous system origin. Am J Pathol 150:805–814
Nakasu S, Nakasu Y, Nioka H, Nakajima M, Handa J (1994) bcl-2 protein expression in tumors of the central nervous system. Acta Neuropathol 88:520–526
Strik H, Deininger M, Streffer J, Grote E, Wickboldt J, Dichgans J, Weller M, Meyermann R (1999) BCL-2 family protein expression in initial and recurrent glioblastomas: modulation by radiochemotherapy. J Neurol Neurosurg Psychiatry 67:763–768
Streffer JR, Rimner A, Rieger J, Naumann U, Rodemann HP, Weller M (2002) BCL-2 family proteins modulate radiosensitivity in human malignant glioma cells. J Neurooncol 56:43–49
Jiang Z, Zheng X, Rich KM (2003) Down-regulation of Bcl-2 and Bcl-xL expression with bispecific antisense treatment in glioblastoma cell lines induce cell death. J Neurochem 84:273–281
Zhu CJ, Li YB, Wong MC (2003) Expression of antisense bcl-2 cDNA abolishes tumorigenicity and enhances chemosensitivity of human malignant glioma cells. J Neurosci Res 74:60–66
Guensberg P, Wacheck V, Lucas T, Monia B, Pehamberger H, Eichler HG, Jansen B (2002) Bcl-xL antisense oligonucleotides chemosensitize human glioblastoma cells. Chemotherapy 48:189–195
Stegh AH, Kim H, Bachoo RM, Forloney KL, Zhang J, Schulze H, Park K, Hannon GJ, Yuan J, Louis DN, DePinho RA, Chin L (2007) BCL-2L12 inhibits post-mitochondrial apoptosis signaling in glioblastoma. Genes Dev 21:98–111
Wagenknecht B, Glaser T, Naumann U, Kügler S, Isenmann S, Bähr M, Korneluk R, Liston P, Weller M (1999) Expression and biological activity of X-linked inhibitor of apoptosis (XIAP) in human malignant glioma. Cell Death Differ 6:370–376
Chen Z, Naito M, Hori S, Mashima T, Yamori T, Tsuruo T (1999) A human IAP-family gene, apollon, expressed in human brain cancer cells. Biochem Biophys Res Commun 264:847–854
Fulda S, Wick W, Weller M, Debatin KM (2002) Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Nat Med 8:808–815
Giagkousiklidis S, Vogler M, Westhoff MA, Kasperczyk H, Debatin KM, Fulda S (2005) Sensitization for gamma-irradiation-induced apoptosis by second mitochondria-derived activator of caspase. Cancer Res 65:10502–10513
Li L, Thomas RM, Suzuki H, De Brabander JK, Wang X, Harran PG (2004) A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death. Science 305:1471–1474
Letai A (2006) Growth factor withdrawal and apoptosis: the middle game. Mol Cell 21:728–730
Broniscer A, Gajjar A (2004) Supratentorial high-grade astrocytoma and diffuse brainstem glioma: two challenges for the pediatric oncologist. Oncologist 9:197–206
Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, Whittle N, Waterfield MD, Ullrich A, Schlessinger J (1985) Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 313:144–147
Fleming TP, Saxena A, Clark WC, Robertson JT, Oldfield EH, Aaronson SA, Ali IU (1992) Amplification and/or overexpression of platelet-derived growth factor receptors and epidermal growth factor receptor in human glial tumors. Cancer Res 52:4550–4553
Hermanson M, Funa K, Hartman M, Claesson-Welsh L, Heldin CH, Westermark B, Nistér M (1992) Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops. Cancer Res 52:3213–3219
Rubin JB, Kung AL, Klein RS, Chan JA, Sun Y, Schmidt K, Kieran MW, Luster AD, Segal RA (2003) A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. Proc Natl Acad Sci U S A 100:13513–13518
Knobbe CB, Reifenberger G (2003) Genetic alterations and aberrant expression of genes related to the phosphatidyl-inositol-3′-kinase/protein kinase B (Akt) signal transduction pathway in glioblastomas. Brain Pathol 13:507–518
Knobbe CB, Trampe-Kieslich A, Reifenberger G (2005) Genetic alteration and expression of the phosphoinositol-3-kinase/Akt pathway genes PIK3CA and PIKE in human glioblastomas. Neuropathol Appl Neurobiol 31:486–490
Smith JS, Tachibana I, Passe SM, Huntley BK, Borell TJ, Iturria N, O’Fallon JR, Schaefer PL, Scheithauer BW, James CD, Buckner JC, Jenkins RB (2001) PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst 93:1246–1256
Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163
Cartron PF, Gallenne T, Bougras G, Gautier F, Manero F, Vusio P, Meflah K, Vallette FM, Juin P (2004) The first alpha helix of Bax plays a necessary role in its ligand-induced activation by the BH3-only proteins Bid and PUMA. Mol Cell 16:807–818
Kuwana T, Mackey MR, Perkins G, Ellisman MH, Latterich M, Schneiter R, Green DR, Newmeyer DD (2002) Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 111:331–342
Breckenridge DG, Xue D (2004) Regulation of mitochondrial membrane permeabilization by BCL-2 family proteins and caspases. Curr Opin Cell Biol 16:647–652
Lutter M, Fang M, Luo X, Nishijima M, Xie X, Wang X (2000) Cardiolipin provides specificity for targeting of tBid to mitochondria. Nat Cell Biol 2:754–761
Lutter M, Perkins GA, Wang X (2001) The pro-apoptotic Bcl-2 family member tBid localizes to mitochondrial contact sites. BMC Cell Biol 2:22
Kim TH, Zhao Y, Ding WX, Shin JN, He X, Seo YW, Chen J, Rabinowich H, Amoscato AA, Yin XM (2004) Bid-cardiolipin interaction at mitochondrial contact site contributes to mitochondrial cristae reorganization and cytochrome C release. Mol Biol Cell 15:3061–3072
Garcia Fernandez M, Troiano L, Moretti L, Nasi M, Pinti M, Salvioli S, Dobrucki J, Cossarizza A (2002) Early changes in intramitochondrial cardiolipin distribution during apoptosis. Cell Growth Differ 13:449–455
Kagan VE, Tyurin VA, Jiang J, Tyurina YY, Ritov VB, Amoscato AA, Osipov AN, Belikova NA, Kapralov AA, Kini V, Vlasova II, Zhao Q, Zou M, Di P, Svistunenko DA, Kurnikov IV, Borisenko GG (2005) Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors. Nat Chem Biol 1:223–232
Chelli B, Lena A, Vanacore R, Da Pozzo E, Costa B, Rossi L, Salvetti A, Scatena F, Ceruti S, Abbracchio MP, Gremigni V, Martini C (2004) Peripheral benzodiazepine receptor ligands: mitochondrial transmembrane potential depolarization and apoptosis induction in rat C6 glioma cells. Biochem Pharmacol 68:125–134
Miettinen H, Kononen J, Haapasalo H, Helén P, Sallinen P, Harjuntausta T, Helin H, Alho H (1995) Expression of peripheral-type benzodiazepine receptor and diazepam binding inhibitor in human astrocytomas: relationship to cell proliferation. Cancer Res 55:2691–2695
Lena A, Rechichi M, Salvetti A, Bartoli B, Vecchio D, Scarcelli V, Amoroso R, Benvenuti L, Gagliardi R, Gremigni V, Rossi L (2009) Drugs targeting the mitochondrial pore act as citotoxic and cytostatic agents in temozolomide-resistant glioma cells. J Transl Med 7:13
Moreno-Sánchez R, Rodríguez-Enríquez S, Saavedra E, Marín-Hernández A, Gallardo-Pérez JC (2009) The bioenergetics of cancer: is glycolysis the main ATP supplier in all tumor cells? Biofactors 35:209–225
Shaw RJ (2006) Glucose metabolism and cancer. Curr Opin Cell Biol 18:598–608
Cuezva JM, Ortega AD, Willers I, Sánchez-Cenizo L, Aldea M, Sánchez-Aragó M (2009) The tumor suppressor function of mitochondria: translation into the clinics. Biochim Biophys Acta 1792:1145–1158
Fulda S (2009) Tumor resistance to apoptosis. Int J Cancer 124:511–515
Kang MH, Reynolds CP (2009) Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy. Clin Cancer Res 15:1126–1132
Berridge MV, Herst PM, Lawen A (2009) Targeting mitochondrial permeability in cancer drug development. Mol Nutr Food Res 53:76–86
Gogvadze V, Zhivotovsky B (2007) Alteration of mitochondrial function and cell sensitization to death. J Bioenerg Biomembr 39:23–30
Kiebish MA, Seyfried TN (2005) Absence of pathogenic mitochondrial DNA mutations in mouse brain tumors. BMC Cancer 5:102
Deighton RF, Mcgregor R, Kemp J, Mcculloch J, Whittle IR (2010) Glioma pathophysiology: insights emerging from proteomics. Brain Pathol (in press)
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Ordys, B.B., Launay, S., Deighton, R.F. et al. The Role of Mitochondria in Glioma Pathophysiology. Mol Neurobiol 42, 64–75 (2010). https://doi.org/10.1007/s12035-010-8133-5
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DOI: https://doi.org/10.1007/s12035-010-8133-5