Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by Zinc

Iwanyshyn, Wendy M.; Han, Gil‐Soo; Carman, George M.

doi:10.1074/jbc.m402047200

Cited by 84 publications

(158 citation statements)

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“…In particular, PI synthase activity is elevated in zinc-depleted cells, whereas several enzyme activities (e.g. PS synthase, PS decarboxylase, PE methyltransferase, and phospholipid methyltransferase) in the CDP-diacylglycerol pathway for PC synthesis are reduced in response to zinc depletion (40). The regulation of these activities by zinc availability contributes to alterations in the cellular levels of the major membrane phospholipids PI (elevated) and PE (reduced) (40).…”

Section: Phosphatidylinositol (Pi)mentioning

confidence: 99%

“…(40) identified PI synthase as an enzyme whose activity increased in wild type cells when zinc was depleted from the growth medium. To confirm that this regulation was governed by the intracellular levels of zinc, the expression of PI synthase activity was examined in a zrt1⌬ zrt2⌬ double mutant (56).…”

Section: Effect Of the Zrt1⌬ Zrt2⌬ Mutations On The Expression Of Pi mentioning

confidence: 99%

“…Recent studies have revealed that the synthesis of phospholipids in S. cerevisiae is influenced by zinc deficiency (40). In particular, PI synthase activity is elevated in zinc-depleted cells, whereas several enzyme activities (e.g.…”

Section: Phosphatidylinositol (Pi)mentioning

confidence: 99%

“…PS synthase, PS decarboxylase, PE methyltransferase, and phospholipid methyltransferase) in the CDP-diacylglycerol pathway for PC synthesis are reduced in response to zinc depletion (40). The regulation of these activities by zinc availability contributes to alterations in the cellular levels of the major membrane phospholipids PI (elevated) and PE (reduced) (40). For the PS synthase enzyme, the reduction in activity in response to zinc depletion is controlled at the level of transcription through the UAS INO element in the CHO1 promoter and by the transcription factors Ino2p, Ino4p, and Opi1p (40).…”

Section: Phosphatidylinositol (Pi)mentioning

confidence: 99%

“…The regulation of these activities by zinc availability contributes to alterations in the cellular levels of the major membrane phospholipids PI (elevated) and PE (reduced) (40). For the PS synthase enzyme, the reduction in activity in response to zinc depletion is controlled at the level of transcription through the UAS INO element in the CHO1 promoter and by the transcription factors Ino2p, Ino4p, and Opi1p (40). In this work, we explored the mechanism by which PI synthase activity is regulated in response to zinc depletion.…”

Section: Phosphatidylinositol (Pi)mentioning

confidence: 99%

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Regulation of the PIS1-encoded Phosphatidylinositol Synthase in Saccharomyces cerevisiae by Zinc

Han

Iwanyshyn

et al. 2005

Journal of Biological Chemistry

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279, 21976 -21983).We examined the effects of zinc depletion on the regulation of the PIS1-encoded phosphatidylinositol synthase, the enzyme that catalyzes the formation of phosphatidylinositol from CDP-diacylglycerol and inositol. Phosphatidylinositol synthase activity increased when zinc was depleted from the growth medium. Analysis of a zrt1⌬ zrt2⌬ mutant defective in plasma membrane zinc transport indicated that the cytoplasmic levels of zinc were responsible for the regulation of phosphatidylinositol synthase. PIS1 mRNA, its encoded protein Pis1p, and the ␤-galactosidase activity driven by the P PIS1 -lacZ reporter gene were elevated in zinc-depleted cells. This indicated that the increase in phosphatidylinositol synthase activity was the result of a transcriptional mechanism. The zinc-mediated induction of the P PIS1 -lacZ reporter gene, Pis1p, and phosphatidylinositol synthase activity was lost in zap1⌬ mutant cells. These data indicated that the regulation of PIS1 gene expression by zinc depletion was mediated by the zinc-regulated transcription factor Zap1p. Direct interaction between glutathione S-transferase (GST)-Zap1p 687-880 and a putative upstream activating sequence (UAS) zinc-responsive element in the PIS1 promoter was demonstrated by electrophoretic mobility shift assays. Mutations in the UAS zinc-responsive element in the PIS1 promoter abolished the GSTZap1p 687-880 -DNA interaction in vitro and abolished the zinc-mediated regulation of the PIS1 gene in vivo. This work advances understanding of phospholipid synthesis regulation by zinc and the transcription control of the PIS1 gene. Phosphatidylinositol (PI)1 is the third most abundant phospholipid in the cellular membranes of the yeast Saccharomyces cerevisiae (1-3), and it is essential for the growth and metabolism of this model eukaryote (4 -6). In addition to being a major structural component of the membrane, PI serves as the precursor for sphingolipids (7,8), the D-3, D-4, and D-5 phosphoinositides (3, 9 -12), and glycosylphosphatidylinositol anchors (13, 14) (Fig. 1). Several of these PI-derived lipids and their metabolic products are prominent signaling molecules in S. cerevisiae and in higher eukaryotes that contribute to essential physiological functions (12,(15)(16)(17)(18)(19)(20).The enzyme responsible for the synthesis of PI in S. cerevisiae is the essential PIS1-encoded PI synthase (CDP-diacylglycerol:myo-inositol 3-phosphatidyltransferase, EC 2.7.8.11) (6, 21-23). This endoplasmic reticulum-associated (24) enzyme catalyzes the formation of PI and CMP from CDP-diacylglycerol and inositol (25) (Fig. 1). The regulation of PI synthase activity in vivo is largely governed by the availability of its substrates inositol and CDP-diacylglycerol (26 -28). Cellular inositol levels are controlled by expression of the INO1 gene encoding inositol-3-phosphate synthase and by inositol supplementation (26 -28). The levels of CDP-diacylglycerol are controlled through its utilization by the PI synthase enzyme itself and the competing activity of ...

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Section: Phosphatidylinositol (Pi)mentioning

confidence: 99%

Section: Effect Of the Zrt1⌬ Zrt2⌬ Mutations On The Expression Of Pi mentioning

confidence: 99%

Section: Phosphatidylinositol (Pi)mentioning

confidence: 99%

Section: Phosphatidylinositol (Pi)mentioning

confidence: 99%

Section: Phosphatidylinositol (Pi)mentioning

confidence: 99%

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Regulation of the PIS1-encoded Phosphatidylinositol Synthase in Saccharomyces cerevisiae by Zinc

Han

Iwanyshyn

et al. 2005

Journal of Biological Chemistry

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ATG15 encodes a phospholipase and is transcriptionally regulated by YAP1 in Saccharomyces cerevisiae

Ramya

Rajasekharan

2016

FEBS Letters

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Edited by Hitoshi NakatogawaPhospholipases play a vital role in maintaining membrane phospholipids. In this study, we found that deletion of the three major phospholipases B in Saccharomyces cerevisiae did not affect the hydrolysis of phospholipids, thus suggesting the presence of other, as yet unidentified, phospholipases. Indeed, in silico analysis of the S. cerevisiae genome identified 13 proteins that contain a conserved, putative serine hydrolase motif. In addition, expression profiling revealed that ATG15 (Autophagy 15) was highly expressed in the phospholipase B triple mutant. ATG15 encodes a phospholipase that preferentially hydrolyzes phosphatidylserine. Our analysis of the ATG15 promoter identified binding sites for Yap1p. In vivo and in vitro results showed that Yap1p positively regulates ATG15 expression. Collectively, we demonstrate that Atg15p is a phosphatidylserine lipase and that Yap1p activates the expression of ATG15 during autophagy.

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Zinc Deficiency Leads to Lipid Changes in Drosophila Brain Similar to Cognitive‐Impairing Drugs: An Imaging Mass Spectrometry Study

Philipsen

Ewing

2020

ChemBioChem

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Several diseases and disorders have been suggested to be associated with zinc deficiency, especially learning and memory impairment. To have better understanding about the connection between lipid changes and cognitive impairments, we investigated the effects of a zinc‐chelated diet on certain brain lipids of Drosophila melanogaster by using time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS). The data revealed that there are increases in the levels of phosphatidylcholine and phosphatidylinositol in the central brains of the zinc‐deficient flies compared to the control flies. In contrast, the abundance of phosphatidylethanolamine in the brains of the zinc‐deficient flies is lower. These data are consistent with that of cognitive‐diminishing drugs, thus providing insight into the biological and molecular effects of zinc deficiency on the major brain lipids and opening a new treatment target for cognitive deficit in zinc deficiency.

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Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by Zinc

Cited by 84 publications

References 135 publications

Regulation of the PIS1-encoded Phosphatidylinositol Synthase in Saccharomyces cerevisiae by Zinc

Regulation of the PIS1-encoded Phosphatidylinositol Synthase in Saccharomyces cerevisiae by Zinc

ATG15 encodes a phospholipase and is transcriptionally regulated by YAP1 in Saccharomyces cerevisiae

Zinc Deficiency Leads to Lipid Changes in Drosophila Brain Similar to Cognitive‐Impairing Drugs: An Imaging Mass Spectrometry Study

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