ATP-binding cassette transporters and cholesterol translocation

Abstract

Cholesterol, a major component of mammalian cell membranes, plays important structural and functional roles. However, accumulation of excessive cholesterol is toxic to cells. Aberrant cholesterol trafficking and accumulation is the molecular basis for many diseases, such as atherosclerotic cardiovascular disease and Tangier's disease. Accumulation of excessive cholesterol is also believed to contribute to the early onset of Alzheimer's disease. Thus, cellular cholesterol homeostasis is tightly regulated by uptake, de novo synthesis, and efflux. Any surplus of cholesterol must either be stored in the cytosol in the form of esters or released from the cell. Recently, several ATP-binding cassette (ABC) transporters, such as ABCA1, ABCG1, ABCG5, and ABCG8 have been shown to play important roles in the regulation of cellular cholesterol homeostasis by mediating cholesterol efflux. Mutations in ABC transporters are associated with several human diseases. In this review, we discuss the physiological roles of ABC transporters and the underlying mechanisms by which they mediate cholesterol translocation.

Keywords: ABC transporters; HDL; LDL; atherosclerosis; cholesterol efflux; membrane proteins.