title: The mitochondrial pyruvate carrier in health and disease: To carry or not to carry?
abstract: Mitochondria play a key role in energy metabolism, hosting the machinery for oxidative phosphorylation, the most efficient cellular pathway for generating ATP. A major checkpoint in this process is the transport of pyruvate produced by cytosolic glycolysis into the mitochondrial matrix, which is accomplished by the recently identified mitochondrial pyruvate carrier (MPC). As the gatekeeper for pyruvate entry into mitochondria, the MPC is thought to be of fundamental importance in establishing the metabolic programming of a cell. This is especially relevant in the context of the aerobic glycolysis, also known as the Warburg effect, which is a hallmark in many types of cancer, and MPC loss of function promotes cancer growth. Moreover, mitochondrial pyruvate uptake is needed for efficient hepatic gluconeogenesis and the regulation of blood glucose levels. In this review we discuss recent advances in our knowledge of the MPC, and we argue that it may offer a promising target in diseases like cancer and type 2 diabetes. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
authors.affiliation: Department of Cell Biology, University of Geneva, 30 quai Ernest-Ansermet, 1211 Genève 4, Switzerland.
authors.forename: Tom
authors.initials: T
authors.lastname: Bender
authors.affiliation: Department of Cell Biology, University of Geneva, 30 quai Ernest-Ansermet, 1211 Genève 4, Switzerland. Electronic address: jean-claude.martinou@unige.ch.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Martinou
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008099:Liver / Q000378:metabolism; D008322:Mammals / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins; D027501:Monocarboxylic Acid Transporters; D009369:Neoplasms / Q000378:metabolism; D010085:Oxidative Phosphorylation; D019289:Pyruvic Acid / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D027321:Anion Transport Proteins; D029721:Drosophila Proteins; C573718:MPC1 protein, human; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D027501:Monocarboxylic Acid Transporters; D029701:Saccharomyces cerevisiae Proteins; D019289:Pyruvic Acid; D005947:Glucose
keywords: Gluconeogenesis; Metabolism; Mitochondria; Mitochondrial pyruvate carrier; Warburg effect