Cellular cholesterol efflux.
Efflux of free cholesterol (FC) continues even when cellular FC mass is unchanged. This reflects a recirculation of preformed FC between cells and extracellular fluids which has multiple functions in cell biology including receptor recycling and signaling as well as cellular FC homeostasis. Total FC efflux is heterogeneous. Simple diffusion to mature high density lipoprotein (HDL), mainly via albumin as intermediate, initiates FC net transport driven by plasma lecithin:cholesterol acyltransferase activity. A second major efflux component reflects protein-facilitated transport from cell surface domains (caveolae, rafts) driven by FC binding to lipid-poor, pre-beta-migrating HDL (pre-beta-HDL). Facilitated efflux from caveolae, unlike simple diffusion, is highly regulated. Neither ABC1 (the protein defective in Tangier disease) nor other ATP-dependent transporters now appear likely to contribute directly to FC efflux. Their role is limited to the initial formation of a particle precursor to circulating pre-beta-HDL, which recycles without further lipid input from ATP-dependent transporter proteins. Lipid-free apolipoprotein A-I, previously considered a surrogate for pre-beta-HDL, has a reactivity much lower than that of native lipoprotein FC acceptors.
Fielding
C J
CJ
Cardiovascular Research Institute and Departments of Physiology and Medicine, Box 0130, University of California Medical Center, San Francisco, CA 94143-0130, USA. cfield@itsa.ucsf.edu
Fielding
P E
PE
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism; D001692:Biological Transport; D001693:Biological Transport, Active; D021941:Caveolae / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D004058:Diffusion; D005089:Exocytosis; D053442:High-Density Lipoproteins, Pre-beta; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008956:Models, Chemical; D010084:Oxidation-Reduction; D011956:Receptors, Cell Surface / Q000378:metabolism; D013379:Substrate Specificity
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D053442:High-Density Lipoproteins, Pre-beta; D008075:Lipoproteins, HDL; D011956:Receptors, Cell Surface; D002784:Cholesterol