title: Tam41 is a CDP-diacylglycerol synthase required for cardiolipin biosynthesis in mitochondria.
abstract: CDP-diacylglycerol (CDP-DAG) is central to the phospholipid biosynthesis pathways in cells. A prevailing view is that only one CDP-DAG synthase named Cds1 is present in both the endoplasmic reticulum (ER) and mitochondrial inner membrane (IM) and mediates generation of CDP-DAG from phosphatidic acid (PA) and CTP. However, we demonstrate here by using yeast Saccharomyces cerevisiae as a model organism that Cds1 resides in the ER but not in mitochondria, and that Tam41, a highly conserved mitochondrial maintenance protein, directly catalyzes the formation of CDP-DAG from PA in the mitochondrial IM. We also find that inositol depletion by overexpressing an arrestin-related protein Art5 partially restores the defects of cell growth and CL synthesis in the absence of Tam41. The present findings unveil the missing step of the cardiolipin synthesis pathway in mitochondria as well as the flexibile regulation of phospholipid biosynthesis to respond to compromised CDP-DAG synthesis in mitochondria.
authors.affiliation: Institute for Advanced Research, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tamura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Harada
authors.forename: Shuh-ichi
authors.initials: S
authors.lastname: Nishikawa
authors.forename: Koji
authors.initials: K
authors.lastname: Yamano
authors.forename: Megumi
authors.initials: M
authors.lastname: Kamiya
authors.forename: Takuya
authors.initials: T
authors.lastname: Shiota
authors.forename: Takuya
authors.initials: T
authors.lastname: Kuroda
authors.forename: Osamu
authors.initials: O
authors.lastname: Kuge
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sesaki
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Imai
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tomii
authors.forename: Toshiya
authors.initials: T
authors.lastname: Endo
mesh_terms: D002308:Cardiolipins / Q000096:biosynthesis* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003567:Cytidine Diphosphate Diglycerides / Q000378:metabolism; D002798:Diacylglycerol Cholinephosphotransferase / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C547820:Art5 protein, S cerevisiae; D002308:Cardiolipins; D002352:Carrier Proteins; D003567:Cytidine Diphosphate Diglycerides; D024101:Mitochondrial Proteins; D010743:Phospholipids; D029701:Saccharomyces cerevisiae Proteins; C514109:TAM41 protein, S cerevisiae; D007294:Inositol; D009713:Nucleotidyltransferases; C022348:phosphatidate cytidylyltransferase; D002798:Diacylglycerol Cholinephosphotransferase