title: Controlling lipid fluxes at glycerol-3-phosphate acyltransferase step in yeast: unique contribution of Gat1p to oleic acid-induced lipid particle formation.
abstract: The ability to channel excess fatty acids into neutral lipids like triacylglycerol (TAG) is a critical strategy used by cells to maintain lipid homeostasis. Upon activation to acyl-CoA, fatty acids become readily available as substrates for acyltransferases involved in neutral lipid synthesis. Neutral lipids are then packed into organelles derived from the endoplasmic reticulum called lipid particles (LPs). The first acylation step in the de novo pathway for TAG synthesis is catalyzed by glycerol-3-phosphate acyltransferases (GPATs). Two isoforms, Gat1p/Gpt2p and Gat2p/Sct1p, are present in the yeast Saccharomyces cerevisiae. Previous evidence indicated that these enzymes contribute differentially to the synthesis of TAG in actively growing cells. In this work we studied the role of the yeast GPATs in the formation of LPs induced by a surplus of oleic acid. Yeast lacking Gat1p (but not Gat2p) were sensitive to oleate and failed to accumulate LPs induced by this unsaturated fatty acid. It is shown that oleate induces dephosphorylation of Gat1p as well as an increment in its levels. Most importantly, we identified novel Gat1p crescent structures that are formed in the presence of oleate. These structures are connected with the endoplasmic reticulum and are intimately associated with LPs. No such structures were observed for Gat2p. A crucial point of control of lipid fluxes at the GPAT step is proposed.
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Marr
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
authors.forename: Julena
authors.initials: J
authors.lastname: Foglia
authors.affiliation: Department of Biological Sciences, University of Toronto at Scarborough, Toronto, Ontario M1C 1A4, Canada, and.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Terebiznik
authors.affiliation: Institute of Biochemistry, Graz University of Technology, A-8010 Graz, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Athenstaedt
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada,. Electronic address: vzarembe@ucalgary.ca.
authors.forename: Vanina
authors.initials: V
authors.lastname: Zaremberg
mesh_terms: D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000235:genetics; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D019301:Oleic Acid / Q000494:pharmacology*; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000235:genetics / Q000378:metabolism*
chemical_list: C096100:GAT1 protein, S cerevisiae; D050980:GATA Transcription Factors; D014280:Triglycerides; D019301:Oleic Acid; D005992:Glycerol-3-Phosphate O-Acyltransferase