Ubiquitin-mediated regulation of sterol homeostasis.

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.