Genome-wide analysis of sterol-lipid storage and trafficking in Saccharomyces cerevisiae

Weihua Fei, Gabriel Alfaro, Baby Periyanayaki Muthusamy, Zachary W A Klaassen, Todd R. Graham, Hongyuan Yang, Christopher T. Beh

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Abstract

The pandemic of lipid-related disease necessitates a determination of how cholesterol and other lipids are transported and stored within cells. The first step in this determination is the identification of the genes involved in these transport and storage processes. Using genome-wide screens, we identified 56 yeast (Saccharomyces cerevisiae) genes involved in sterol-lipid biosynthesis, intracellular trafficking, and/or neutral-lipid storage. Direct biochemical and cytological examination of mutant cells revealed an unanticipated link between secretory protein glycosylation and triacylglycerol (TAG)/steryl ester (SE) synthesis for the storage of lipids. Together with the analysis of other deletion mutants, these results suggested at least two distinct events for the biogenesis of lipid storage particles: a step affecting neutral-lipid synthesis, generating the lipid core of storage particles, and another step for particle assembly. In addition to the lipid storage mutants, we identified mutations that affect the localization of unesterified sterols, which are normally concentrated in the plasma membrane. These findings implicated phospholipase C and the protein phosphatase Ptc1p in the regulation of sterol distribution within cells. This study identified novel sterol-related genes that define several distinct processes maintaining sterol homeostasis.

Original languageEnglish (US)
Pages (from-to)401-414
Number of pages14
JournalEukaryotic Cell
Volume7
Issue number2
DOIs
StatePublished - Feb 1 2008

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Sterols
Saccharomyces cerevisiae
Genome
Lipids
Genes
Phosphoprotein Phosphatases
Type C Phospholipases
Pandemics
Glycosylation
Esters
Triglycerides
Homeostasis
Yeasts
Cholesterol
Cell Membrane
Mutation

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Genome-wide analysis of sterol-lipid storage and trafficking in Saccharomyces cerevisiae. / Fei, Weihua; Alfaro, Gabriel; Muthusamy, Baby Periyanayaki; Klaassen, Zachary W A; Graham, Todd R.; Yang, Hongyuan; Beh, Christopher T.

In: Eukaryotic Cell, Vol. 7, No. 2, 01.02.2008, p. 401-414.

Research output: Contribution to journalArticle

Fei, W, Alfaro, G, Muthusamy, BP, Klaassen, ZWA, Graham, TR, Yang, H & Beh, CT 2008, 'Genome-wide analysis of sterol-lipid storage and trafficking in Saccharomyces cerevisiae', Eukaryotic Cell, vol. 7, no. 2, pp. 401-414. https://doi.org/10.1128/EC.00386-07
Fei, Weihua ; Alfaro, Gabriel ; Muthusamy, Baby Periyanayaki ; Klaassen, Zachary W A ; Graham, Todd R. ; Yang, Hongyuan ; Beh, Christopher T. / Genome-wide analysis of sterol-lipid storage and trafficking in Saccharomyces cerevisiae. In: Eukaryotic Cell. 2008 ; Vol. 7, No. 2. pp. 401-414.
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