Regulation of HMG-CoA reductase in mammals and yeast

John S. Burg, Peter J. Espenshade

Research output: Contribution to journalReview article

Abstract

HMG-CoA reductase (HMGR), a highly conserved, membrane-bound enzyme, catalyzes a rate-limiting step in sterol and isoprenoid biosynthesis and is the primary target of hypocholesterolemic drug therapy. HMGR activity is tightly regulated to ensure maintenance of lipid homeostasis, disruption of which is a major cause of human morbidity and mortality. HMGR regulation takes place at the levels of transcription, translation, post-translational modification and degradation. In this review, we discuss regulation of mammalian, Saccharomyces cerevisiae and Schizosaccharomyces pombe HMGR and highlight recent advances in the field. We find that the general features of HMGR regulation, including a requirement for the HMGR-binding protein Insig, are remarkably conserved between mammals and ascomycetous fungi, including S. cerevisiae and S. pombe. However the specific details by which this regulation occurs differ in surprising ways, revealing the broad evolutionary themes underlying both HMGR regulation and Insig function.

Original languageEnglish (US)
Pages (from-to)403-410
Number of pages8
JournalProgress in Lipid Research
Volume50
Issue number4
DOIs
StatePublished - Oct 2011

Keywords

  • AMPK
  • ERAD
  • HMG-CoA reductase
  • HRD
  • Insig
  • Sterol

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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