Recent advances in membrane cholesterol domain dynamics and intracellular cholesterol trafficking

Friedhelm Schroeder, Andrey A. Frolov, Eric J. Murphy, Barbara P. Atshaves, John R. Jefferson, Lixia Pu, W. Gibson Wood, William B. Foxworth, Ann B. Kier

Research output: Contribution to journalReview articlepeer-review

131 Scopus citations

Abstract

Cholesterol is distributed nonrandomly in and between biological membranes. Despite over two decades' investigation of those phenomena, the origin, regulation, and function of membrane cholesterol asymmetry are not known. Likewise, although pathways of cellular cholesterol absorption/utilization as well as de novo synthesis have been investigated in depth, parallel progress in elucidating pathways of intracellular cholesterol trafficking and final deposition of cholesterol within membranes remains undefined. Understanding the nature and regulation of those processes is essential to resolving molecular mechanisms of cholesterol uptake, reverse cholesterol transport, steroidogenesis, and modulation of membrane function. Based on the fundamental observation that cholesterol is not distributed uniformly in the cell, three key concepts have contributed to recent advances in this field: First, cholesterol is asymmetrically distributed across the cell surface plasma membrane, wherein it translocates rapidly. Second, cholesterol is distributed within the plane of biomembrane bilayers into dynamic and static domains, with the latter predominating. The exact nature and physiological functions of such cholesterol domains or pools remain an enigma. Third, regulation of the size and kinetics of biomembrane cholesterol domains may be determining factors in intracellular cholesterol trafficking, targeting, and efflux. Contributions of both cytosolic carrier proteins and vesicular processes are recognized.

Original languageEnglish (US)
Pages (from-to)150-177
Number of pages28
JournalProceedings of the Society for Experimental Biology and Medicine
Volume213
Issue number2
DOIs
StatePublished - Nov 1996

Bibliographical note

Funding Information:
This work was supported in part by grants from the U.S. Public Health Service (GM31651 to F. S.; AG11056 to W. G. W.), the Medical Research Service of the Department of Veterans Affairs (to W. G. W.), and the Research Corporation Cottrell College Science Award C3501 (J. R. I.). 11 1996 213 2 150 177

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