Membrane Biology Group
Bose lab program
My laboratory is interested in the folding and translocation of mitochondrial proteins that regulate steroid hormone synthesis. These proteins are encoded by nuclear genes, synthesized in the cytoplasm, and imported into mitochondria. The general mechanisms of mitochondrial import have been well studied and involve a proteinaceous channel composed of several proteins on the inner and outer mitochondrial membranes.
Among the proteins imported into mitochondria are enzymes that convert cholesterol into steroid hormones. The steroidogenic acute regulatory protein (StAR), a phosphoprotein, facilitates the movement of cholesterol from the outer to inner mitochondrial membrane. Human StAR mutations cause a lethal disorder of steroidogenesis, and an equivalent phenotype is seen in StAR knockout mice. The unusual behavior of StAR, coupled with some unusual features of StAR's import kinetics suggested that the mechanism of StAR's import may be distinct from that of other mitochondrial proteins. My laboratory's goal is to characterize StAR's and StAR like protein(s) entry into mitochondria: to understand StAR's docking with the OMM, to determine whether it enters the mitochondria through a non-classic import channel, to identify proteins in that channel and to characterize how StAR enters. In addition we seek to understand how StAR binds to, imports, and discharges cholesterol, and how the process of StAR-mediated cholesterol import is related to StAR's protein import.
In the similar line, we seek to understand translocation mechanism of 3bhydroxysteroid dehydrogenase, another mitochondrial protein that participates in a many different steps of tissue specific steroid production.
Aldosterone synthase converts deoxycorticosterone to the steroid aldosterone, which regulates blood volume. Overproduction of aldosterone can lead to hypertension, a condition that is linked to heart disease and stroke. We are currently studying the mechanism of aldosterone synthase localization to the mitochondria, and how this process is regulated.