Organelle plasticity and interactions in cholesterol transport and steroid biosynthesis

Steroid biosynthesis is a multi-step process controlled by pituitary hormones, which, via cAMP-dependent signaling pathways, drive tissue-specific steroid formation. Steroidogenesis begins with the transport of the substrate, cholesterol, from intracellular stores into the inner mitochondrial membrane, where the steroidogenic enzyme CYP11A1 converts cholesterol to pregnenolone. This process is accelerated by hormones and involves a number of proteins and protein-protein interactions. Indeed, cholesterol, stored in lipid droplets and membranes, is transferred through a hormone-induced complex of proteins derived from the cytosol, mitochondria, and other organelles termed the transduceosome to the outer mitochondrial membrane. From there, cholesterol reaches CYP11A1 through outer/inner membrane contact sites. Thus, cholesterol transfer is likely achieved through a hormone-dependent reorganization of organelles and protein distribution and interactions. The findings reviewed herein suggest the presence of a hormone-dependent organelle communication network mediated by protein-protein interactions and inter-organelle trafficking, resulting in the efficient and timely delivery of cholesterol into mitochondria for steroid synthesis.