title: Monocarboxylate transporters in the brain and in cancer.
abstract: Monocarboxylate transporters (MCTs) constitute a family of 14 members among which MCT1-4 facilitate the passive transport of monocarboxylates such as lactate, pyruvate and ketone bodies together with protons across cell membranes. Their anchorage and activity at the plasma membrane requires interaction with chaperon protein such as basigin/CD147 and embigin/gp70. MCT1-4 are expressed in different tissues where they play important roles in physiological and pathological processes. This review focuses on the brain and on cancer. In the brain, MCTs control the delivery of lactate, produced by astrocytes, to neurons, where it is used as an oxidative fuel. Consequently, MCT dysfunctions are associated with pathologies of the central nervous system encompassing neurodegeneration and cognitive defects, epilepsy and metabolic disorders. In tumors, MCTs control the exchange of lactate and other monocarboxylates between glycolytic and oxidative cancer cells, between stromal and cancer cells and between glycolytic cells and endothelial cells. Lactate is not only a metabolic waste for glycolytic cells and a metabolic fuel for oxidative cells, but it also behaves as a signaling agent that promotes angiogenesis and as an immunosuppressive metabolite. Because MCTs gate the activities of lactate, drugs targeting these transporters have been developed that could constitute new anticancer treatments. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
authors.affiliation: Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCL), Avenue Emmanuel Mounier 52 box B1.53.09, 1200 Brussels, Belgium.
authors.forename: Jhudit
authors.initials: J
authors.lastname: Pérez-Escuredo
authors.affiliation: Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCL), Avenue Emmanuel Mounier 52 box B1.53.09, 1200 Brussels, Belgium.
authors.forename: Vincent F
authors.initials: VF
authors.lastname: Van Hée
authors.affiliation: Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCL), Avenue Emmanuel Mounier 52 box B1.53.09, 1200 Brussels, Belgium.
authors.forename: Martina
authors.initials: M
authors.lastname: Sboarina
authors.affiliation: Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCL), Avenue Emmanuel Mounier 52 box B1.53.09, 1200 Brussels, Belgium.
authors.forename: Jorge
authors.initials: J
authors.lastname: Falces
authors.affiliation: Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCL), Avenue Emmanuel Mounier 52 box B1.53.09, 1200 Brussels, Belgium.
authors.forename: Valéry L
authors.initials: VL
authors.lastname: Payen
authors.affiliation: Laboratory of Neuroenergetics, Department of Physiology, University of Lausanne, Rue du Bugnon 7, 1005 Lausanne, Switzerland. Electronic address: luc.pellerin@unil.ch.
authors.forename: Luc
authors.initials: L
authors.lastname: Pellerin
authors.affiliation: Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCL), Avenue Emmanuel Mounier 52 box B1.53.09, 1200 Brussels, Belgium. Electronic address: pierre.sonveaux@uclouvain.be.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sonveaux
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001693:Biological Transport, Active; D001921:Brain / Q000378:metabolism*; D001927:Brain Diseases / Q000378:metabolism; D003071:Cognition / Q000502:physiology; D005786:Gene Expression Regulation; D006019:Glycolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007657:Ketone Bodies / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009928:Organ Specificity; D010085:Oxidative Phosphorylation; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats
chemical_list: D007657:Ketone Bodies; D007773:Lactates; D027501:Monocarboxylic Acid Transporters; D009363:Neoplasm Proteins; D019289:Pyruvic Acid
keywords: Astrocytes; Lactate shuttle; Metabolic cooperation; Neurons; Tumor cells; Tumor microenvironment