title: Mitochondrial dysfunctions in cancer: genetic defects and oncogenic signaling impinging on TCA cycle activity.
abstract: The tricarboxylic acid (TCA) cycle is a central route for oxidative metabolism. Besides being responsible for the production of NADH and FADH2, which fuel the mitochondrial electron transport chain to generate ATP, the TCA cycle is also a robust source of metabolic intermediates required for anabolic reactions. This is particularly important for highly proliferating cells, like tumour cells, which require a continuous supply of precursors for the synthesis of lipids, proteins and nucleic acids. A number of mutations among the TCA cycle enzymes have been discovered and their association with some tumour types has been established. In this review we summarise the current knowledge regarding alterations of the TCA cycle in tumours, with particular attention to the three germline mutations of the enzymes succinate dehydrogenase, fumarate hydratase and isocitrate dehydrogenase, which are involved in the pathogenesis of tumours, and to the aberrant regulation of TCA cycle components that are under the control of oncogenes and tumour suppressors.
authors.affiliation: Department of Biology, University of Rome "Tor Vergata", Via della Ricerca Scientifica, 00133 Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Desideri
authors.affiliation: Department of Biology, University of Rome "Tor Vergata", Via della Ricerca Scientifica, 00133 Rome, Italy.
authors.forename: Rolando
authors.initials: R
authors.lastname: Vegliante
authors.affiliation: Department of Biology, University of Rome "Tor Vergata", Via della Ricerca Scientifica, 00133 Rome, Italy; IRCCS San Raffaele Pisana, Via di Val Cannuta, 00166 Rome, Italy. Electronic address: ciriolo@bio.uniroma2.it.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Ciriolo
mesh_terms: D000154:Aconitate Hydratase / Q000096:biosynthesis; D049109:Cell Proliferation / Q000502:physiology; D002952:Citric Acid Cycle / Q000235:genetics* / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics*; D005649:Fumarate Hydratase / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008291:Malate Dehydrogenase / Q000096:biosynthesis; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010085:Oxidative Phosphorylation; D064828:Prolyl Hydroxylases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D015398:Signal Transduction / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D008291:Malate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D064828:Prolyl Hydroxylases; D013385:Succinate Dehydrogenase; D017346:Protein Serine-Threonine Kinases; D005649:Fumarate Hydratase; D000154:Aconitate Hydratase
keywords: Aconitase; Fumarate hydratase; HIF; Isocitrate dehydrogenase; Succinate dehydrogenase; p53