title: Phosphatidate phosphatase plays role in zinc-mediated regulation of phospholipid synthesis in yeast.
abstract: In the yeast Saccharomyces cerevisiae, the synthesis of phospholipids is coordinately regulated by mechanisms that control the homeostasis of the essential mineral zinc (Carman, G.M., and Han, G. S. (2007) Regulation of phospholipid synthesis in Saccharomyces cerevisiae by zinc depletion. Biochim. Biophys. Acta 1771, 322-330; Eide, D. J. (2009) Homeostatic and adaptive responses to zinc deficiency in Saccharomyces cerevisiae. J. Biol. Chem. 284, 18565-18569). The synthesis of phosphatidylcholine is balanced by the repression of CDP-diacylglycerol pathway enzymes and the induction of Kennedy pathway enzymes. PAH1-encoded phosphatidate phosphatase catalyzes the penultimate step in triacylglycerol synthesis, and the diacylglycerol generated in the reaction may also be used for phosphatidylcholine synthesis via the Kennedy pathway. In this work, we showed that the expression of PAH1-encoded phosphatidate phosphatase was induced by zinc deficiency through a mechanism that involved interaction of the Zap1p zinc-responsive transcription factor with putative upstream activating sequence zinc-responsive elements in the PAH1 promoter. The pah1Δ mutation resulted in the derepression of the CHO1-encoded phosphatidylserine synthase (CDP-diacylglycerol pathway enzyme) and loss of the zinc-mediated regulation of the enzyme. Loss of phosphatidate phosphatase also resulted in the derepression of the CKI1-encoded choline kinase (Kennedy pathway enzyme) but decreased the synthesis of phosphatidylcholine when cells were deficient of zinc. This result confirmed the role phosphatidate phosphatase plays in phosphatidylcholine synthesis via the Kennedy pathway.
authors: Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey 08901, USA.
authors: Aníbal
authors: A
authors: Soto-Cardalda
authors: Stylianos
authors: S
authors: Fakas
authors: Florencia
authors: F
authors: Pascual
authors: Hyeon-Son
authors: HS
authors: Choi
authors: George M
authors: GM
authors: Carman
mesh_terms: D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase / Q000096:biosynthesis / Q000235:genetics; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D010711:Phosphatidate Phosphatase / Q000096:biosynthesis* / Q000235:genetics; D010713:Phosphatidylcholines / Q000096:biosynthesis* / Q000235:genetics; D020218:Response Elements / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
chemical_list: C490519:CHO1 protein, S cerevisiae; D010713:Phosphatidylcholines; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C103264:ZAP1 protein, S cerevisiae; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase; C079831:PAH1 protein, S cerevisiae; D010711:Phosphatidate Phosphatase; D015032:Zinc