Molecular mechanisms generating and maintaining phospholipid asymmetry and its consequences.

Cholesterol is an essential molecule for human life. However, excess cholesterol is associated with a variety of pathologies most notably heart disease. The organization and distribution of cholesterol is influenced by a variety of protein as well as other fats. The distribution and organization of these fats are regulated by a variety of proteins, referred to as scramblases and flippases. Not surprisingly, mutations in these proteins are proposed to influence a myriad of disorders including male infertility, bile acid accumulation in the liver, diabetes, obesity and neurological defects. This proposal will explore both the cell biological roles of phosphatidylserine and the proteins that regulate its distribution and their impact on the distribution of cholesterol within the cell. Understanding the function of this lipid within the cell and the proteins that regulate it will help us understand the disorders described and aid in the development of treatments.