STEROIDOGENIC ACUTE REGULATORY PROTEIN (STAR) IS A STEROL TRANSFER PROTEIN

Steroidogenic acute regulatory protein (StAR) plays a critical role in steroidogenesis by enhancing the delivery of substrate cholesterol fr om the outer mitochondrial membrane to the cholesterol side chain clea vage enzyme system on the inner membrane. A recombinant StAR protein l acking the first N-terminal 62 amino acid residues that includes the m itochondrial targeting sequence was shown to stimulate the transfer of cholesterol and beta-sitosterol from liposomes to heat-treated mitoch ondria in a dose-, time-, and temperature-dependent manner. A recombin ant mutant StAR protein that cannot stimulate steroidogenesis by isola ted mitochondria did not promote sterol transfer. Unlike the more prom iscuous lipid transfer protein, sterol carrier protein 2 (SCP2), StAR did not stimulate phosphatidylcholine transfer in our assay system. Th e recombinant StAR protein increased cholesterol transfer to heat-trea ted microsomes as well as to heat- and trypsin-treated mitochondria. T hese observations demonstrate that StAR has sterol transfer activity, which may reflect an ability to enhance desorption of cholesterol from sterol-rich donor membranes. We suggest that the ability of StAR to p romote sterol transfer explains its steroidogenic activity.