Role of Cholesterol in Maintaining Asymmetric Distribution of Phosphatidylserine in Plasma Membranes

Abstract Cholesterol, an essential lipid component of plasma membranes, regulates membrane fluidity and the formation of lipid rafts. Phospholipids are asymmetrically distributed between the lipid bilayer in plasma membranes; notably, phosphatidylserine (a bioactive phospholipid) is distributed solely in the inner leaflet. However, its distribution is disrupted (exposed to the outer leaflet) during cell death and several other cellular reactions. Recent studies have shown that cholesterol has a novel function in regulating the asymmetric distribution of phosphatidylserine. In this chapter, we explain the physiological significance and regulatory mechanisms of phosphatidylserine distribution in human erythrocytes (see Section 2 ), with an in-depth understanding of its relation to cholesterol, and further examine this more concisely in platelets (see Section 3 ) and apoptotic cells (see Section 4 ), with a discussion on the latest findings. Finally, we discuss an innate evolutionary insurance against the complete loss of flippase activity, and the appropriate selection of scramblases in these 3 cell types.