title: Cancer cell metabolism and mitochondria: Nutrient plasticity for TCA cycle fueling.
abstract: Warburg's hypothesis that cancer cells take up a lot of glucose in the presence of ambient oxygen but convert pyruvate into lactate due to impaired mitochondrial function led to the misconception that cancer cells rely on glycolysis as their major source of energy. Most recent13C-based metabolomic studies, including in cancer patients, indicate that cancer cells may also fully oxidize glucose. In addition to glucose-derived pyruvate, lactate, fatty acids and amino acids supply substrates to the TCA cycle to sustain mitochondrial metabolism. Here, we discuss how the metabolic flexibility afforded by these multiple mitochondrial inputs allows cancer cells to adapt according to the availability of the different fuels and the microenvironmental conditions such as hypoxia and acidosis. In particular, we focused on the role of the TCA cycle in interconnecting numerous metabolic routes in order to highlight metabolic vulnerabilities that represent attractive targets for a new generation of anticancer drugs.
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, 53 Avenue Mounier B1.53.09, B-1200 Brussels, Belgium.
authors.forename: Cyril
authors.initials: C
authors.lastname: Corbet
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, 53 Avenue Mounier B1.53.09, B-1200 Brussels, Belgium. Electronic address: olivier.feron@uclouvain.be.
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
mesh_terms: D000138:Acidosis / Q000378:metabolism / Q000473:pathology; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002952:Citric Acid Cycle / Q000502:physiology*; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D000596:Amino Acids
keywords: Fatty acid; Glucose; Glutamine; Metabolism; Mitochondria; Tumor