Identification and functional expression of the mitochondrial pyruvate carrier.
The transport of pyruvate, the end product of glycolysis, into mitochondria is an essential process that provides the organelle with a major oxidative fuel. Although the existence of a specific mitochondrial pyruvate carrier (MPC) has been anticipated, its molecular identity remained unknown. We report that MPC is a heterocomplex formed by two members of a family of previously uncharacterized membrane proteins that are conserved from yeast to mammals. Members of the MPC family were found in the inner mitochondrial membrane, and yeast mutants lacking MPC proteins showed severe defects in mitochondrial pyruvate uptake. Coexpression of mouse MPC1 and MPC2 in Lactococcus lactis promoted transport of pyruvate across the membrane. These observations firmly establish these proteins as essential components of the MPC.
Department of Cell Biology, University of Geneva, Geneva, Switzerland.
Sébastien
S
Herzig
Etienne
E
Raemy
Sylvie
S
Montessuit
Jean-Luc
JL
Veuthey
Nicola
N
Zamboni
Benedikt
B
Westermann
Edmund R S
ER
Kunji
Jean-Claude
JC
Martinou
D000595:Amino Acid Sequence; D000818:Animals; D027321:Anion Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D053898:Biosynthetic Pathways; D003470:Culture Media; D013294:Lactococcus lactis / Q000235:genetics / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D008969:Molecular Sequence Data; D027501:Monocarboxylic Acid Transporters; D045664:Proprotein Convertase 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045706:Proprotein Convertase 2; D019289:Pyruvic Acid / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008063:Thioctic Acid / Q000096:biosynthesis / Q000378:metabolism; D014633:Valine / Q000378:metabolism
D027321:Anion Transport Proteins; D003470:Culture Media; C573715:FMP37 protein, S cerevisiae; C573717:FMP43 protein, S cerevisiae; C573716:MPC2 protein, S cerevisiae; D033681:Mitochondrial Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D008063:Thioctic Acid; D019289:Pyruvic Acid; C473656:Pcsk1 protein, mouse; D045664:Proprotein Convertase 1; C473668:Pcsk2 protein, mouse; D045706:Proprotein Convertase 2; D007930:Leucine; D014633:Valine