Regulation of lipid/sterol flux in endocytic and exocytic pathways by oxysterol binding proteins

Cells are composed of discrete compartments called organelles (for example, the mitochondria) that are surrounded by membranes composed of lipids and cholesterol. There is a steady flow or exchange of lipids and cholesterol between organelles that is essential for their activity. Lipid and cholesterol movement between organelles can occur by several different processes, one of which involves attachment to a protein that then moves the lipid between the organelles. This proposal is to study one such class of 'transport proteins' called OSBPs that move specific types of lipids and cholesterol. We will identify which specific lipids these OSBPs move between organelles, and the effect of blocking this transfer on the activity of the organelle. We will also characterize a human genetic mutation in an OSBP that causes abnormal accumulation of lipids in cells. These studies will provide fundamental insights into the role of these lipid transfer proteins in cells, and their importance in prevention of abnormal accumulation of cholesterol and other lipids that contribute to disease.