title: Na(+)/H(+) antiporter (NHE1) and lactate/H(+) symporters (MCTs) in pH homeostasis and cancer metabolism.
abstract: The Na(+)/H(+)-exchanger NHE1 and the monocarboxylate transporters MCT1 and MCT4 are crucial for intracellular pH regulation, particularly under active metabolism. NHE1, a reversible antiporter, uses the energy provided by the Na(+) gradient to expel H(+) ions generated in the cytosol. The reversible H(+)/lactate(-) symporters MCT1 and 4 cotransport lactate and proton, leading to the net extrusion of lactic acid in glycolytic tumors. In the first two sections of this article we review important features and remaining questions on the structure, biochemical function and cellular roles of these transporters. We then use a fully-coupled mathematical model to simulate their relative contribution to pH regulation in response to lactate production, as it occurs in highly hypoxic and glycolytic tumor cells. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
authors.affiliation: University of Nice-Sophia Antipolis, LP2M UMR7370, Faculty of Medicine, 28 Avenue Valombrose, 06107 Nice France; Laboratories of Excellence Ion Channel Science and Therapeutics, France. Electronic address: Laurent.Counillon@unice.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Counillon
authors.affiliation: University of Nice-Sophia Antipolis, LPMC UMR 7336, 28 Avenue Valrose, 06108 Nice, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Bouret
authors.affiliation: IRCAN, Centre A. Lacassagne, University of Nice-Sophia Antipolis, 33 Avenue Valombrose, 06107 Nice, France.
authors.forename: Ibtissam
authors.initials: I
authors.lastname: Marchiq
authors.affiliation: IRCAN, Centre A. Lacassagne, University of Nice-Sophia Antipolis, 33 Avenue Valombrose, 06107 Nice, France; Centre Scientifique de Monaco (CSM), 8, Quai Antoine 1er, Monaco. Electronic address: pouysseg@unice.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Pouysségur
mesh_terms: D001693:Biological Transport, Active; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006019:Glycolysis; D006706:Homeostasis; D006801:Humans; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport; D019344:Lactic Acid / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D027501:Monocarboxylic Acid Transporters / Q000502:physiology*; D009124:Muscle Proteins / Q000502:physiology*; D009154:Mutation; D009363:Neoplasm Proteins / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism*; D011487:Protein Conformation; D012964:Sodium / Q000378:metabolism*; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D027981:Symporters / Q000502:physiology*; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D027682:Cation Transport Proteins; D006859:Hydrogen; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D012964:Sodium; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C406962:SLC16A4 protein, human; C490998:SLC9A1 protein, human
keywords: Cancer; Lactate transporters; MCTs; Mathematical model; Membrane transporters; NHE1; pH regulation