title: Phosphatidylserine transport by Ups2-Mdm35 in respiration-active mitochondria.
abstract: Phosphatidylethanolamine (PE) is an essential phospholipid for mitochondrial functions and is synthesized mainly by phosphatidylserine (PS) decarboxylase at the mitochondrial inner membrane. In Saccharomyces cerevisiae, PS is synthesized in the endoplasmic reticulum (ER), such that mitochondrial PE synthesis requires PS transport from the ER to the mitochondrial inner membrane. Here, we provide evidence that Ups2-Mdm35, a protein complex localized at the mitochondrial intermembrane space, mediates PS transport for PE synthesis in respiration-active mitochondria. UPS2- and MDM35-null mutations greatly attenuated conversion of PS to PE in yeast cells growing logarithmically under nonfermentable conditions, but not fermentable conditions. A recombinant Ups2-Mdm35 fusion protein exhibited phospholipid-transfer activity between liposomes in vitro. Furthermore, UPS2 expression was elevated under nonfermentable conditions and at the diauxic shift, the metabolic transition from glycolysis to oxidative phosphorylation. These results demonstrate that Ups2-Mdm35 functions as a PS transfer protein and enhances mitochondrial PE synthesis in response to the cellular metabolic state.
authors.affiliation: Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka 819-0395, Japan.
authors.forename: Non
authors.identifier: 0000-0002-5945-909X
authors.initials: N
authors.lastname: Miyata
authors.affiliation: Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Material and Biological Chemistry, Faculty of Science, Yamagata University, Yamagata 990-8560, Japan.
authors.forename: Yasushi
authors.identifier: 0000-0002-8462-0607
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Endo
authors.affiliation: Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka 819-0395, Japan kuge@chem.kyushu-univ.jp.
authors.forename: Osamu
authors.identifier: 0000-0003-4962-3519
authors.initials: O
authors.lastname: Kuge
mesh_terms: D001692:Biological Transport; D019069:Cell Respiration; D005285:Fermentation; D017353:Gene Deletion; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C552370:Mdm35 protein, S cerevisiae; D024101:Mitochondrial Proteins; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D029701:Saccharomyces cerevisiae Proteins; C542159:Ups2 protein, S cerevisiae; C483858:phosphatidylethanolamine