Pleiotropic effects of the opil regulatory mutation of yeast: its effects on growth and on phospholipid and inositol metabolism

Jiranek, Vladimir; Graves, James; Henry, Susan A.

doi:10.1099/00221287-144-10-2739

Cited by 35 publications

(41 citation statements)

References 42 publications

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“…However, in contrast to the zinc-mediated effect on PE content, stationary phase has little effect on PE (124). Thus, whereas zinc depletion and stationary phase (124,125,132) regulated enzyme expression through the UAS INO element, these stress conditions yielded different effects on phospholipid composition.…”

Section: Discussionmentioning

confidence: 80%

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Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by Zinc

Iwanyshyn

Han

Carman

2004

Journal of Biological Chemistry

156

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Zinc is an essential nutrient required for the growth and metabolism of eukaryotic cells. In this work, we examined the effects of zinc depletion on the regulation of phospholipid synthesis in the yeast Saccharomyces cerevisiae. Zinc depletion resulted in a decrease in the activity levels of the CDP-diacylglycerol pathway enzymes phosphatidylserine synthase, phosphatidylserine decarboxylase, phosphatidylethanolamine methyltransferase, and phospholipid methyltransferase. In contrast, the activity of phosphatidylinositol synthase was elevated in response to zinc depletion. The level of Aut7p, a marker for the induction of autophagy, was also elevated in zinc-depleted cells. For the CHO1-encoded phosphatidylserine synthase, the reduction in activity in response to zinc depletion was controlled at the level of transcription. This regulation was mediated through the UAS INO element and by the transcription factors Ino2p, Ino4p, and Opi1p that are responsible for the inositol-mediated regulation of UAS INO -containing genes involved in phospholipid synthesis. Analysis of the cellular composition of the major membrane phospholipids showed that zinc depletion resulted in a 66% decrease in phosphatidylethanolamine and a 29% increase in phosphatidylinositol. A zrt1⌬ zrt2⌬ mutant (defective in the plasma membrane zinc transporters Zrt1p and Zrt2p) grown in the presence of zinc exhibited a phospholipid composition similar to that of wild type cells depleted for zinc. These results indicated that a decrease in the cytoplasmic levels of zinc was responsible for the alterations in phospholipid composition.

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Section: Discussionmentioning

confidence: 80%

“…The UAS INO -containing genes and their enzyme products are repressed when cells enter the stationary phase of growth (124,125,132). Cells enter this growth phase and stop proliferating when essential nutrients (e.g.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by Zinc

Iwanyshyn

Han

Carman

2004

Journal of Biological Chemistry

156

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“…To test this possibility, we assayed the effect of several NuA4 component mutants on expression of an OPI1-cat reporter ( Figure 4C). As reported, the expression of the OPI1-cat reporter was repressed twofold by the addition of inositol and choline ( Jiranek et al 1998;Wagner et al 1999;Lopes 2003, 2006). However, the NuA4 component mutants did not yield reduced expression of the OPI1-cat reporter.…”

Section: A Genomewide Screen Identified 89 Opimentioning

confidence: 87%

Genomic Analysis of the Opi− Phenotype

2006

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Most of the phospholipid biosynthetic genes of Saccharomyces cerevisiae are coordinately regulated in response to inositol and choline. Inositol affects the intracellular levels of phosphatidic acid (PA). Opi1p is a repressor of the phospholipid biosynthetic genes and specifically binds PA in the endoplasmic reticulum. In the presence of inositol, PA levels decrease, releasing Opi1p into the nucleus where it represses transcription. The opi1 mutant overproduces and excretes inositol into the growth medium in the absence of inositol and choline (Opi À phenotype). To better understand the mechanism of Opi1p repression, the viable yeast deletion set was screened to identify Opi À mutants. In total, 89 Opi À mutants were identified, of which 7 were previously known to have the Opi À phenotype. The Opi À mutant collection included genes with roles in phospholipid biosynthesis, transcription, protein processing/synthesis, and protein trafficking. Included in this set were all nonessential components of the NuA4 HAT complex and six proteins in the Rpd3p-Sin3p HDAC complex. It has previously been shown that defects in phosphatidylcholine synthesis (cho2 and opi3) yield the Opi À phenotype because of a buildup of PA. However, in this case the Opi À phenotype is conditional because PA can be shuttled through a salvage pathway (Kennedy pathway) by adding choline to the growth medium. Seven new mutants present in the Opi À collection ( fun26, kex1, nup84, tps1, mrpl38, mrpl49, and opi10/yol032w) were also suppressed by choline, suggesting that these affect PC synthesis. Regulation in response to inositol is also coordinated with the unfolded protein response (UPR). Consistent with this, several Opi À mutants were found to affect the UPR (yhi9, ede1, and vps74).

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“…Opi1p homologues in S. cerevisiae, C. albicans, and Yarrowia lipolytica (Yas3p) are not essential (Hirakawa et al, 2009;Jiranek et al, 1998) (Y. L. Chen & T. B. Reynolds, unpublished). It is of interest to note that in S. cerevisiae and C. glabrata, two closely related yeasts, the Opi1p proteins both regulate inositol biosynthesis, whereas in the more distantly related yeasts C. albicans and Y. lipolytica, their Opi1p family members, CaOpi1p (C. We are currently investigating the mechanism by which CgOPI1 controls viability in C. glabrata.…”

Section: Discussionmentioning

confidence: 99%

“…The regulation of ScINO1 in response to extracellular inositol is dependent on the repressor protein ScOpi1p (Heyken et al, 2005;Jiranek et al, 1998;Loewen et al, 2003Loewen et al, , 2004Loewen & Levine, 2005). ScOpi1p senses the level of extracellular inositol indirectly based on the level of the PI precursor lipid phosphatidic acid (PA).…”

Section: Introductionmentioning

confidence: 99%

The inositol regulon controls viability in Candida glabrata

et al. 2010

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Inositol is essential in eukaryotes, and must be imported or synthesized. Inositol biosynthesis in Saccharomyces cerevisiae is controlled by three non-essential genes that make up the inositol regulon: ScINO2 and ScINO4, which together encode a heterodimeric transcriptional activator, and ScOPI1, which encodes a transcriptional repressor. ScOpi1p inhibits the ScIno2-ScIno4p activator in response to extracellular inositol levels. An important gene controlled by the inositol regulon is ScINO1, which encodes inositol-3-phosphate synthase, a key enzyme in inositol biosynthesis. In the pathogenic yeast Candida albicans, homologues of the S. cerevisiae inositol regulon genes are ‘transcriptionally rewired’. Instead of regulating the CaINO1 gene, CaINO2 and CaINO4 regulate ribosomal genes. Another Candida species that is a prevalent cause of infections is Candida glabrata; however, C. glabrata is phylogenetically more closely related to S. cerevisiae than C. albicans. Experiments were designed to determine if C. glabrata homologues of the inositol regulon genes function similarly to S. cerevisiae or are transcriptionally rewired. CgINO2, CgINO4 and CgOPI1 regulate CgINO1 in a manner similar to that observed in S. cerevisiae. However, unlike in S. cerevisiae, CgOPI1 is essential. Genetic data indicate that CgOPI1 is a repressor that affects viability by regulating activation of a target of the inositol regulon.

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Pleiotropic effects of the opil regulatory mutation of yeast: its effects on growth and on phospholipid and inositol metabolism

Cited by 35 publications

References 42 publications

Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by Zinc

Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by Zinc

Genomic Analysis of the Opi− Phenotype

The inositol regulon controls viability in Candida glabrata

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