title: Mitochondrial pyruvate carrier in Trypanosoma brucei.
abstract: Pyruvate is a key product of glycolysis that regulates the energy metabolism of cells. In Trypanosoma brucei, the causative agent of sleeping sickness, the fate of pyruvate varies dramatically during the parasite life cycle. In bloodstream forms, pyruvate is mainly excreted, whereas in tsetse fly forms, pyruvate is metabolized in mitochondria yielding additional ATP molecules. The character of the molecular machinery that mediates pyruvate transport across mitochondrial membrane was elusive until the recent discovery of mitochondrial pyruvate carrier (MPC) in yeast and mammals. Here, we characterized pyruvate import into mitochondrion of T. brucei. We identified mpc1 and mpc2 homologs in the T. brucei genome with attributes of MPC protein family and we demonstrated that both proteins are present in the mitochondrial membrane of the parasite. Investigations of mpc1 or mpc2 gene knock-out cells proved that T. brucei MPC1/2 proteins facilitate mitochondrial pyruvate transport. Interestingly, MPC is expressed not only in procyclic trypanosomes with fully activated mitochondria but also in bloodstream trypanosomes in which most of pyruvate is excreted. Moreover, MPC appears to be essential for bloodstream forms, supporting the recently emerging picture that the functions of mitochondria in bloodstream forms are more diverse than it was originally thought.
authors.affiliation: Department of Parasitology, Faculty of Science, Charles University in Prague, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Štáfková
authors.affiliation: Department of Parasitology, Faculty of Science, Charles University in Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Mach
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques (RMSB), UMR5536 CNRS.
authors.forename: Marc
authors.initials: M
authors.lastname: Biran
authors.affiliation: Department of Parasitology, Faculty of Science, Charles University in Prague, Czech Republic.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Verner
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques (RMSB), UMR5536 CNRS.|Laboratoire de Microbiologie Fondamentale et Pathogénicité (MFP), UMR5234 CNRS, Université de Bordeaux, Bordeaux, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bringaud
authors.affiliation: Department of Parasitology, Faculty of Science, Charles University in Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Tachezy
mesh_terms: D000595:Amino Acid Sequence; D027321:Anion Transport Proteins / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D002460:Cell Line; D004734:Energy Metabolism / Q000502:physiology; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters; D019289:Pyruvic Acid / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism*
chemical_list: D027321:Anion Transport Proteins; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D019289:Pyruvic Acid