Sphingomyelin depletion impairs anionic phospholipid inward translocation and induces cholesterol efflux

Abstract

Background: Phosphatidylserine floppase activity of ABCA1 is required for optimal cholesterol efflux, as demonstrated via a floppase-impaired ABCA1 mutation. Results: Sphingomyelin depletion compensates for floppase-impaired ABCA1 and increases cell surface phosphatidylserine. Conclusion: Sphingomyelin depletion inhibits flip of anionic phospholipids and thus promotes cholesterol efflux. Significance: Flippase inhibition may serve as a novel drug target to increase cholesterol efflux. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.