Abstract:
The precise physiological roles of the ancient and conserved membrane protein TSPO (otherwise known as the translocator protein 18kD or the peripheral benzodiazepine receptor) remain obscure. The original discovery of TSPO in mammals occurred when it was found as an additional binding site for benzodiazepine drugs. High expression in tissues involved in steroid hormone synthesis along with other evidence suggested a regulatory role in cholesterol uptake into mitochondria, especially under stress conditions. More recently, TSPO knockout mouse models show inconsistent characteristics that weaken this hypothesis, although some common features exist: the loss of TSPO increased lipid oxidation, decreased ATP synthesis and decreased mitochondrial membrane potential. Another common feature of TSPO across all kingdoms appears to be the ability to bind porphyrins, including heme and protoporphyrin IX, likely endogenous ligands. Yet despite decades of research, there is no consensus regarding the nature and mechanism of TSPO effects. In this talk, I will discuss the current state of the structural, biochemical, and physiological analyses that are beginning to reveal how TSPO functions.