Cholesterol sulfate as a negative regulator of cellular cholesterol homeostasis.

ABSTRACT: Cholesterol sulfate (CS), one of the most abundant cholesterol derivatives, recently emerged as a key regulatory molecule in several physiological processes. Here, we demonstrate multiple mechanisms by which CS reduces intracellular cholesterol levels. CS promotes the proteasomal degradation of 3-hydroxy-3-methylglutaryl-CoA reductase reductase by enhancing insulin-induced gene-mediated ubiquitination, thereby inhibiting cholesterol synthesis. In addition, CS blocks low-density lipoprotein receptor endocytosis, reducing low-density lipoprotein cholesterol uptake. CS further suppresses the proteolytic activation of sterol regulatory element-binding protein 2, a master transcription factor governing cholesterol synthesis and uptake. Using in vitro and in vivo models, we show that CS lowers c

SUBMITTER: Nam LB 

PROVIDER: S-EPMC12182261 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature