title: Phosphatidate phosphatase activity plays key role in protection against fatty acid-induced toxicity in yeast.
abstract: The PAH1-encoded phosphatidate (PA) phosphatase in Saccharomyces cerevisiae is a pivotal enzyme that produces diacylglycerol for the synthesis of triacylglycerol (TAG) and simultaneously controls the level of PA used for phospholipid synthesis. Quantitative lipid analysis showed that the pah1Δ mutation caused a reduction in TAG mass and an elevation in the mass of phospholipids and free fatty acids, changes that were more pronounced in the stationary phase. The levels of unsaturated fatty acids in the pah1Δ mutant were unaltered, although the ratio of palmitoleic acid to oleic acid was increased with a similar change in the fatty acid composition of phospholipids. The pah1Δ mutant exhibited classic hallmarks of apoptosis in stationary phase and a marked reduction in the quantity of cytoplasmic lipid droplets. Cells lacking PA phosphatase were sensitive to exogenous fatty acids in the order of toxicity palmitoleic acid > oleic acid > palmitic acid. In contrast, the growth of wild type cells was not inhibited by fatty acid supplementation. In addition, wild type cells supplemented with palmitoleic acid exhibited an induction in PA phosphatase activity and an increase in TAG synthesis. Deletion of the DGK1-encoded diacylglycerol kinase, which counteracts PA phosphatase in controlling PA content, suppressed the defect in lipid droplet formation in the pah1Δ mutant. However, the sensitivity of the pah1Δ mutant to palmitoleic acid was not rescued by the dgk1Δ mutation. Overall, these findings indicate a key role of PA phosphatase in TAG synthesis for protection against fatty acid-induced toxicity.
authors.affiliation: Department of Food Science, Rutgers University, New Brunswick, New Jersey 08901; Department of Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey 08901 and.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Fakas
authors.affiliation: Department of Food Science, Rutgers University, New Brunswick, New Jersey 08901; Department of Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey 08901 and.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Nutritional Sciences, Rutgers University, New Brunswick, New Jersey 08901; Department of Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey 08901 and.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Dixon
authors.affiliation: Department of Food Science, Rutgers University, New Brunswick, New Jersey 08901; Department of Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey 08901 and.
authors.forename: Gil-Soo
authors.initials: GS
authors.lastname: Han
authors.affiliation: Department of Pediatrics and Institute of Human Nutrition, Columbia University Medical Center, New York, New York 10032.
authors.forename: Kelly V
authors.initials: KV
authors.lastname: Ruggles
authors.affiliation: Department of Pediatrics and Institute of Human Nutrition, Columbia University Medical Center, New York, New York 10032.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Garbarino
authors.affiliation: Department of Pediatrics and Institute of Human Nutrition, Columbia University Medical Center, New York, New York 10032.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Sturley
authors.affiliation: Department of Food Science, Rutgers University, New Brunswick, New Jersey 08901; Department of Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey 08901 and. Electronic address: carman@aesop.rutgers.edu.
authors.forename: George M
authors.initials: GM
authors.lastname: Carman
mesh_terms: D017209:Apoptosis / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism*; D009154:Mutation; D010711:Phosphatidate Phosphatase / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D005227:Fatty Acids; D029701:Saccharomyces cerevisiae Proteins; D014280:Triglycerides; C079831:PAH1 protein, S cerevisiae; D010711:Phosphatidate Phosphatase