Abstract
We have studied the movement of low density lipoprotein (LDL)-derived cholesterol in cultured Chinese hamster ovary cells. Our hypothesis is that when LDL cholesterol is effluxed from lysosomes, the bulk of LDL cholesterol is mobilized to the plasma membrane, while another pathway delivers LDL cholesterol from lysosomes to acyl-CoA/cholesterol acyltransferase (ACAT) in the endoplasmic reticulum. Three lines of evidence support this model. First, LDL cholesterol transport to ACAT can be blocked without inhibiting the movement of cholesterol from lysosomes to plasma membrane or from plasma membrane to endoplasmic reticulum. Second, LDL cholesterol transport to ACAT is normal in a Chinese hamster ovary mutant with defective plasma membrane-to-ACAT movement. Third, LDL cholesterol is not diluted by the plasma membrane cholesterol pool before reaching ACAT. Our evidence supports a vesicular model of cholesterol transport from lysosomes to the endoplasmic reticulum that is independent of the plasma membrane.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amphotericin B / pharmacology
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Androstenes / pharmacology
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Animals
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Biological Transport / drug effects
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Biological Transport / physiology
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Brefeldin A
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CHO Cells
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Cell Membrane / physiology*
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Cholesterol Esters / metabolism
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Cholesterol Oxidase / metabolism
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Cholesterol, LDL / metabolism*
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Cricetinae
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Cyclopentanes / pharmacology
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Endoplasmic Reticulum / enzymology*
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Enzyme Inhibitors / pharmacology
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Imipramine / pharmacology
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Lipoproteins, LDL / metabolism
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Lysosomes / physiology*
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Microscopy, Fluorescence
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Oleic Acid / metabolism
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Sphingomyelin Phosphodiesterase / antagonists & inhibitors
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Sphingomyelin Phosphodiesterase / metabolism
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Sterol O-Acyltransferase / metabolism
Substances
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Androstenes
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Cholesterol Esters
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Cholesterol, LDL
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Cyclopentanes
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Enzyme Inhibitors
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Lipoproteins, LDL
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Brefeldin A
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Oleic Acid
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3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one
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Amphotericin B
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Cholesterol Oxidase
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Sterol O-Acyltransferase
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Sphingomyelin Phosphodiesterase
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Imipramine