Transport of lipids by ABC proteins: Interactions and implications for cellular toxicity, viability and function

Members of the ATP-binding cassette (ABC) family of membrane-bound transporters are involved in multipleaspects of transport and redistribution of various lipids and their conjugates. Most ABC transporterslocalize to the plasmamembrane; some are associated with liquid-ordered cholesterol-/sphingolipid-richmicrodomains, and to a lesser extent the membranes of the Golgi and endoplasmic reticulum. Hence, ABCtransporters are well placed to regulate plasma membrane lipid composition and the efflux and redistributionof structural phospholipids and sphingolipids during periods of cellular stress and recovery. ABCtransporters can also modulate cellular sensitivity to extrinsic pro-apoptotic signals through regulation ofsphingomyelin–ceramide biosynthesis and metabolism. The functionality of ABC transporters is, in turn,modulated by the lipid content of the microdomains in which they reside. Cholesterol, a major membranemicrodomain component, is not only a substrate of several ABC transporters, but also regulatesABC activity through its effects on microdomain structure. Several important bioactive lipid mediatorsand toxic lipid metabolites are also effluxed by ABC transporters. In this review, the complex interactionsbetween ABC transporters and their lipid/sterol substrates will be discussed and analyzed in the contextof their relevance to cellular function, toxicity and apoptosis.© 2009 Elsevier Ireland Ltd. All rights reserved.