Ubiquitin-mediated regulation of sterol homeostasis

Curr Opin Cell Biol. 2020 Aug:65:103-111. doi: 10.1016/j.ceb.2020.04.010. Epub 2020 Jun 21.

Abstract

Cholesterol is an essential component of mammalian membranes, and its homeostasis is strictly regulated, with imbalances causing atherosclerosis, Niemann Pick disease, and familial hypercholesterolemia. Cellular cholesterol supply is mediated by LDL-cholesterol import and de novo cholesterol biosynthesis, and both pathways are adjusted to cellular demand by the cholesterol-sensitive SREBP2 transcription factor. Cholesterol homeostasis is modulated by a wide variety of metabolic pathways and the ubiquitination machinery, in particular E3 ubiquitin ligases. In this article, we review recent progress in understanding the role of E3 ubiquitin ligases in the metabolic control of cellular sterol homeostasis.

Keywords: Cholesterol; E3 ubiquitin ligases; ER associated degradation (ERAD); HMG-CoA reductase; LDL-cholesterol import; RNF145; SCAP; SREBP2; Sterol-induced HMGCR degradation; Ubiquitin-mediated cholesterol homeostasis; gp78.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Homeostasis*
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / genetics
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Proteolysis
  • Sterols / metabolism*
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Sterols
  • Ubiquitin
  • Hydroxymethylglutaryl CoA Reductases
  • Ubiquitin-Protein Ligases