Cellular cholesterol substrate pools for adenosine-triphosphate cassette transporter A1-dependent high-density lipoprotein formation.
OBJECTIVE
The removal of cellular cholesterol and phospholipids to apolipoprotein A-I (apoA-I), facilitated by the membrane transporter ATP-binding cassette transporter A1 (ABCA1), is the rate-limiting step in the formation of high density lipoprotein particles. This review summarizes recent literature concerning the relative contributions of different cellular pools of cholesterol used by ABCA1 in the initial lipidation of apoA-I for high density lipoprotein particle formation.


RESULTS
Cell culture studies have shown that apart from lipidating apoA-I directly, ABCA1 can also mediate cholesterol delivery indirectly to apoA-I in the plasma membrane. Moreover, it is now clear that the late endosome/lysosome pool of cholesterol is a critical part of the total cholesterol substrate pool for ABCA1. Internalization of ABCA1 appears to be a requirement for maximum ABCA1-mediated cholesterol mobilization for high density lipoprotein formation.


CONCLUSIONS
Current evidence suggests that ABCA1-mediated cholesterol efflux to apoA-I involves mobilization of cholesterol from plasma membrane, endoplasmic reticulum, trans-Golgi network, late endocytic and lysosomal compartments, and cholesteryl ester droplets. Apart from lipidating apoA-I directly, ABCA1 has also been found to efflux cholesterol indirectly to apoA-I in plasma membranes.
Boadu
Emmanuel
E
The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research and Division of Endocrinology and Metabolism, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Bilbey
Nicolas J
NJ
Francis
Gordon A
GA
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D015388:Organelles / Q000378:metabolism
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D002784:Cholesterol