The Sterol-Specific Regulation Of Acat-1 And Srebps In Mammalian Cells And In Liver

Within a single cell, low-density lipoprotein receptor (LDLR), 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, and Acyl-coenzyme A: cholesterol acyltransferase (ACAT) are three of the major cellular components that control intracellular cholesterol homeostasis. The main mode of sterol-specific regulation of ACAT is at the post-translational level, while a major mode of regulation of LDLR, HMG-CoA reductase, and various other cholesterologenic enzymes is at the transcriptional level; transcription control involves a pair of sterol-regulated protein factors called sterol regulatory element binding proteins (SREBPs). In this chapter, we summarize the molecular studies that suggest how sterol may act to regulate ACAT and SREBPs. We also summarize the current knowledge on the suggested physiological roles of ACAT and SREBPs in livers of intact animals.