Specific cellular microenvironments for spatiotemporal regulation of StAR and steroid synthesis

CASTILLO, ANA FERNANDA; PODEROSO, CECILIA; MALOBERTI, PAULA MARIANA; CORNEJO MACIEL, FABIANA; MORI SEQUEIROS GARCIA, MARÍA MERCEDES; ORLANDO, ULISES DANIEL; MELE, PABLO; BENZO, YANINA; DATTILO, MELINA ANDREA; PRADA, JESICA; QUEVEDO, LUCIANO; BELLUNO, MATÍAS; PAZ, CRISTINA; PODESTA, ERNESTO JORGE

JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Año: 2024

0022-0795

For many years, research in the field of steroid synthesis has aimed to understand the regulation of the rate-limiting step of steroid synthesis, i.e., the transport of cholesterol from the outer to the inner mitochondrial membrane, and identify the protein involved in the conversion of cholesterol into pregnenolone. The extraordinary work by B Clark, J Wells, S R King, and D M Stocco eventually identified this protein and named it steroidogenic acute regulatory protein (StAR). The group’s finding was also one of the milestones in understanding the mechanism of non-vesicular lipid transport between organelles. A notable feature of StAR is its high degree of phosphorylation. In fact, StAR phosphorylation in the acute phase is required for full steroid biosynthesis. As a contribution to this subject, our work has led to the characterization of StAR as a substrate of kinases and phosphatases and as an integral part of a mitochondria-associated multi-protein complex, essential for StAR function and cholesterol binding and mitochondrial transport to yield maximum steroid production. Results allow us to postulate the existence of a specific cellular microenvironment where StAR protein synthesis and activation, along with steroid synthesis and secretion, are performed in a compartmentalized manner, at the site of hormone receptor stimulation, and involving the compartmentalized formation of the steroid molecule synthesizing complex