The role of lipid scramblases in regulating lipid distributions at cellular membranes

Glycerophospholipids, sphingolipids and cholesterol assemble into lipid bilayers that form the scaffold of cellular membranes, in which proteins are embedded. Membrane composition and membrane protein profiles differ between plasma and intracellular membranes and between the two leaflets of a membrane. Lipid distributions between two leaflets are mediated by lipid translocases, including flippases and scramblases. Flippases use ATP to catalyze the inward movement of specific lipids between leaflets. In contrast, bidirectional flip-flop movements of lipids across the membrane are mediated by scramblases in an ATP-independent manner. Scramblases have been implicated in disrupting the lipid asymmetry of the plasma membrane, protein glycosylation, autophagosome biogenesis, lipoprotein secretion, lipid droplet formation and communications between organelles. Although scramblases in plasma membranes were identified over 10 years ago, most progress about scramblases localized in intracellular membranes has been made in the last few years. Herein, we review the role of scramblases in regulating lipid distributions in cellular membranes, focusing primarily on intracellular membrane-localized scramblases.

Automated summary

Glycerophospholipids, sphingolipids and cholesterol form the scaffold of cellular membranes, with proteins embedded in them. Lipid translocases, including flippases and scramblases, mediate the distribution of lipids in the membrane, with flippases moving specific lipids between leaflets using ATP and scramblases facilitating bidirectional flip-flop movements of lipids across the membrane in an ATP-independent manner. Scramblases play important roles in regulating lipid distribution in cellular membranes and are involved in various cellular processes.