Plasma membrane cholesterol trafficking in steroidogenesis.

ABSTRACT: Cholesterol is an important component of plasma membranes (PMs) and the precursor of all steroid hormones. In steroidogenic tissues, upon hormone stimulation, there is a rapid transfer of cholesterol to the mitochondria, which is the site of the initial step in steroidogenesis. In the current study, we examined PM cholesterol trafficking for steroidogenesis. In a mitochondrial reconstitution assay, adrenal PMs supported steroidogenesis in the absence of additional transport proteins. Depletion of cholesterol in PMs by 50% eliminated the membranes' ability to support steroidogenesis in vitro and reduced steroid production in intact Y1 adrenocortical cells. Syntaxin (STX)-5 and ?-soluble N-ethylmaleimide-sensitive factor attachment protein (?-SNAP) are enriched in adrenal PMs, and adrenocorticotropic hormone treatment of rats recruited STX5 and ?-SNAP to adrenal PMs and mitochondria. Immunodepletion of STX5 and ?-SNAP from PMs decreased steroidogenesis supported by PMs in vitro. Protease digestion of PMs decreased, whereas recombinant STX5 or ?-SNAP restored, the PMs' ability to support steroidogenesis. Knockdown of either STX5 or ?-SNAP in Y1 cells decreased stimulated steroidogenesis. These results indicate that STX5 and ?-SNAP facilitate cholesterol trafficking from PMs to mitochondria for adrenal steroid synthesis and underscore the importance of vesicular trafficking of PM cholesterol for steroidogenesis.-Deng, B., Shen, W.-J., Dong, D., Azhar, S., Kraemer, F. B. Plasma membrane cholesterol trafficking in steroidogenesis.

SUBMITTER: Deng B 

PROVIDER: S-EPMC6988844 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature