title: Intramitochondrial transport of phosphatidic acid in yeast by a lipid transfer protein.
abstract: Mitochondria are dynamic organelles whose function depends on intramitochondrial phospholipid synthesis and the supply of membrane lipids from the endoplasmic reticulum. How phospholipids are transported to and in-between mitochondrial membranes remained unclear. We identified Ups1, a yeast member of a conserved family of intermembrane space proteins, as a lipid transfer protein that can shuttle phosphatidic acid between mitochondrial membranes. Lipid transfer required the dynamic assembly of Ups1 with Mdm35 and allowed conversion of phosphatidic acid to cardiolipin in the inner membrane. High cardiolipin concentrations prevented membrane dissociation of Ups1, leading to its proteolysis and inhibiting transport of phosphatidic acid and cardiolipin synthesis. Thus, intramitochondrial lipid trafficking may involve a regulatory feedback mechanism that limits the accumulation of cardiolipin in mitochondria.
authors.affiliation: Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Connerth
authors.forename: Takashi
authors.initials: T
authors.lastname: Tatsuta
authors.forename: Mathias
authors.initials: M
authors.lastname: Haag
authors.forename: Till
authors.initials: T
authors.lastname: Klecker
authors.forename: Benedikt
authors.initials: B
authors.lastname: Westermann
authors.forename: Thomas
authors.initials: T
authors.lastname: Langer
mesh_terms: D001692:Biological Transport; D002308:Cardiolipins / Q000096:biosynthesis / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D025461:Feedback, Physiological; D008081:Liposomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002308:Cardiolipins; D002352:Carrier Proteins; D008081:Liposomes; C552370:Mdm35 protein, S cerevisiae; D024101:Mitochondrial Proteins; D010712:Phosphatidic Acids; D010743:Phospholipids; D029701:Saccharomyces cerevisiae Proteins; C512497:Ups1 protein, S cerevisiae; C030363:lipid transfer protein