RECENT ADVANCES IN MEMBRANE CHOLESTEROL DOMAIN DYNAMICS AND INTRACELLULAR CHOLESTEROL TRAFFICKING

Cholesterol is distributed nonrandomly in and between biological membr anes, Despite over two decades' investigation of these phenomena, the origin, regulation, and function of membrane cholesterol asymmetry are not known, Likewise, although pathways of cellular cholesterol absorp tion/utilization as well as de novo synthesis have been investigated i n depth, parallel progress in elucidating pathways of intracellular ch olesterol trafficking and final deposition of cholesterol within membr anes remains undefined, Understanding the nature and regulation of the se processes is essential to resolving molecular mechanisms of cholest erol uptake, reverse cholesterol transport, steroidogenesis, and modul ation of membrane function, Based on the fundamental observation that cholesterol is not distributed uniformly in the cell, three key concep ts have contributed to recent advances in this field: First, cholester ol is asymmetrically distributed across the cell surface plasma membra ne, wherein it translocates rapidly. Second, cholesterol is distribute d within the plane of biomembrane bilayers into dynamic and static dom ains, with the latter predominating, The exact nature and physiologica l functions of such cholesterol domains or pools remain an enigma, Thi rd, regulation of the size and kinetics of biomembrane cholesterol dom ains may be determining factors in intracellular cholesterol trafficki ng, targeting, and efflux, Contributions of both cytosolic carrier pro teins and vesicular processes are recognized.