Structure, function and regulation of the mitochondrial peripheral-type benzodiazepine receptor

Steroid biosynthesis begins with the transfer of cholesterol from intracellular stores into mitochondria. Through in vitro and in vivo studies using various steroidogenic cell models and with the help of pharmacological, biochemical, morphological and molecular approaches we demonstrated that the peripheral-type benzodiazepine receptor (PBR) is an 18 kDa mitochondrial protein that interacts with other proteins in the outer mitochondrial membrane to form a multimeric complex. PBR is required for the binding, uptake and release, upon ligand activation, of the substrate cholesterol. Thus, cholesterol becomes available to the inner mitochondrial membrane P450scc where steroid biosynthesis begins. The presence of mitochondrial PBR is also critical in maintaining outer mitochondrial membrane stability and in preventing apoptosis. Considering these functions of PBR and the fact that PBR is a ubiquitous protein, it is suggested that this drug receptor may serve as a target to control various mitochondrial and cell functions and to protect against experimentally or pathologically induced mitochondrial and cell toxicity.