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Genome-wide screen for inositol auxotrophy in Saccharomyces cerevisiae implicates lipid metabolism in stress response signaling

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Abstract

Inositol auxotrophy (Ino− phenotype) in budding yeast has classically been associated with misregulation of INO1 and other genes involved in lipid metabolism. To identify all non-essential yeast genes that are necessary for growth in the absence of inositol, we carried out a genome-wide phenotypic screening for deletion mutants exhibiting Ino− phenotypes under one or more growth conditions. We report the identification of 419 genes, including 385 genes not previously reported, which exhibit this phenotype when deleted. The identified genes are involved in a wide range of cellular processes, but are particularly enriched in those affecting transcription, protein modification, membrane trafficking, diverse stress responses, and lipid metabolism. Among the Ino− mutants involved in stress response, many exhibited phenotypes that are strengthened at elevated temperature and/or when choline is present in the medium. The role of inositol in regulation of lipid metabolism and stress response signaling is discussed.

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Abbreviations

Ino− :

Inositol auxotrophy

RNA-Pol II:

RNA polymerase II

PI:

Phosphatidylinositol

PA:

Phosphatidic acid

ER:

Endoplasmic reticulum

DAG:

Diacylglycerol

PC:

Phosphatidylcholine

PKC–CWI:

Protein kinase C–cell wall integrity

UPR:

Unfolded protein response

AMPK:

AMP-dependant kinase

HOG:

High osmolarity glycerol

ERAD:

ER-associated protein degradation

TOR:

Target of rapamycin

PKA:

cAMP-protein kinase A

MAPK:

Mitogen activated protein kinase

ORF:

Open reading frame

GO:

Gene Ontology

SGD:

Saccharomyces genome database

YPD:

1% yeast extract, 2% bactopeptone, 2% glucose

I:

Inositol

C:

Choline

GroPCho:

Glycerol-phospho-choline

GPI:

Glycosylphosphatidylinositol

Gro-3-P:

Glycerol-3-phosphate

lyso-PA:

Lyso-phosphatidic acid

DHA:

Dihydroxyacetone

DHAP:

Dihydroxyacetone phosphate

PIP:

Phosphoinositides

IP3 :

Inositol 1,4,5-triphosphate

IPC:

Inositol-phosphorylceramide

MIPC:

Mannosyl-inositol-phosphorylceramide

M(IP)2C:

Mannosyl-diinositol-phosphorylceramide

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Ackowledgments

This work was supported by National Institutes of Health Grant GM019629 (to SAH.)

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  1. Department of Molecular Biology and Genetics, Cornell University, 249 Biotechnology Building, Ithaca, NY, 14853, USA

    Manuel J. Villa-García, Myung Sun Choi, Flora I. Hinz, María L. Gaspar, Stephen A. Jesch & Susan A. Henry

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  1. Manuel J. Villa-García
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  2. Myung Sun Choi
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  3. Flora I. Hinz
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  4. María L. Gaspar
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  5. Stephen A. Jesch
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  6. Susan A. Henry
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Correspondence to Susan A. Henry.

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Communicated by S. Hohmann.

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Villa-García, M.J., Choi, M.S., Hinz, F.I. et al. Genome-wide screen for inositol auxotrophy in Saccharomyces cerevisiae implicates lipid metabolism in stress response signaling. Mol Genet Genomics 285, 125–149 (2011). https://doi.org/10.1007/s00438-010-0592-x

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