Project: Endolysosomal cholesterol trafficking, steroidogenesis and human pathophysiology

About

Steroid hormones are lipophilic molecules that play a critical role in endocrine function and in metabolic, immune, and nervous system regulation. They are synthesized in the mitochondria of steroidogenic tissues from a common precursor, cholesterol, which must be present in large quantities and in continuous flux in specialized cells to meet the physiological needs of the organism throughout life. Because mitochondria are relatively poor in cholesterol, cholesterol must be transported from intracellular sites to replenish its supply in the outer mitochondrial membrane and then transferred to the inner mitochondrial membrane for conversion to steroids. Factors and processes suggested to contribute to cholesterol trafficking to steroidogenic mitochondria involve putative lipid transport proteins and vesicular processes, although the exact mechanisms are not fully understood. With a focus on the specific role of the endolysosomal compartment, this research aims to understand how cholesterol is transported to mitochondria to be used in steroidogenesis. A better understanding of this intracellular trafficking could have crucial clinical implications, as an alteration of this process could be at the origin of hormone-dependent pathologies and tumors in humans.