Cholesterol Delivery From the Plasma Membrane To the ER Is the Rate Limiting Factor of Acyl-Coenzyme A Acyltransferase Activity In Vivo
(English)Manuscript (preprint) (Other academic)
Intracellular free cholesterol accumulation is toxic and has to be avoided. Acyl-CoA: cholesterol acyltransferase (ACAT) clears cells of cholesterol by forming cholesteryl esters (CE). Upon cold stress of Jurkat T cells at 0°C, plasma membrane cholesterol is reduced and both CEs and lipid droplets accumulate rapidly, resembling cells acutely loaded with exogenous cholesterol. ACAT is responsible for the increase, determined using the ACAT inhibitor Sandoz 58035. Cold stress accumulation of CEs requires the redistribution of plasma membrane cholesterol, shown by acute methyl-beta-cyclodextrin mediated cholesterol depletion. Filipin staining revealed that ACAT inhibition resulted in increased plasma membrane cholesterol levels. The plasma membrane of both cold stressed and cholesterol-loaded cells contained a lower proportion of ordered domains than control cells, assessed by laurdan staining. In vivo ACAT is limited by ER cholesterol availability that can be increased by redistribution of endogenous cholesterol.
ACAT, Cholesterol, Plasma membrane, Cholesteryl esters
Cell and Molecular Biology
Research subject Cellbiology
IdentifiersURN: urn:nbn:se:su:diva-38350OAI: oai:DiVA.org:su-38350DiVA: diva2:309876