Regulation of sterol synthesis in eukaryotes

Peter Espenshade, Adam L. Hughes

Research output: Contribution to journalArticle

Abstract

Cholesterol is an essential component of mammalian cell membranes and is required for proper membrane permeability, fluidity, organelle identity, and protein function. Cells maintain sterol homeostasis by multiple feedback controls that act through transcriptional and posttranscriptional mechanisms. The membrane-bound transcription factor sterol regulatory element binding protein (SREBP) is the principal regulator of both sterol synthesis and uptake. In mammalian cells, the ER membrane protein Insig has emerged as a key component of homeostatic regulation by controlling both the activity of SREBP and the sterol-dependent degradation of the biosynthetic enzyme HMG-CoA reductase. In this review, we focus on recent advances in our understanding of the molecular mechanisms of the regulation of sterol synthesis. A comparative analysis of SREBP and HMG-CoA reductase regulation in mammals, yeast, and flies points toward an equilibrium model for how lipid signals regulate the activity of sterol-sensing proteins and their downstream effectors.

Original languageEnglish (US)
Pages (from-to)401-427
Number of pages27
JournalAnnual Review of Genetics
Volume41
DOIs
StatePublished - 2007

Fingerprint

Sterols
Eukaryota
Sterol Regulatory Element Binding Proteins
Hydroxymethylglutaryl CoA Reductases
Membrane Fluidity
Organelles
Mammals
Permeability
Membrane Proteins
Proteins
Homeostasis
Transcription Factors
Yeasts
Cholesterol
Cell Membrane
Lipids
Membranes
Enzymes

Keywords

  • Cholesterol synthesis
  • Endoplasmic reticulum
  • HMG-CoA reductase
  • Insig
  • Scap
  • SREBP
  • Yeast

ASJC Scopus subject areas

  • Genetics

Cite this

Regulation of sterol synthesis in eukaryotes. / Espenshade, Peter; Hughes, Adam L.

In: Annual Review of Genetics, Vol. 41, 2007, p. 401-427.

Research output: Contribution to journalArticle

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