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Abstract
Cholesterol homeostasis is essential for the functional integrity of the cell (1). Both the cellular content and distribution of cholesterol within the cell is highly dynamic and tightly regulated through de novo synthesis of cholesterol by the endoplasmic reticulum (ER) (2), and by uptake of cholesterol ester-rich lipoprotein particles circulating in the serum by the low-density lipoprotein (LDL) receptor pathway (3). The main sorting station for cholesterol within the cell is the late endosome (LE), an intermediate stage in the endosomal-lysosomal trafficking pathway (Fig. 1). LEs are also referred to as “multivesicular” compartments in that they have numerous internalized membrane-enveloped structures generated by the ESCRT pathway (4) (Fig. 1). Within the lumen of the LE, cholesterol esters are hydrolyzed to free cholesterol by acid lipase. Released cholesterol joins the endogenous cholesterol pool for recycling to the cell surface, or transferred to the ER where they are re-esterified and, as necessary, placed in storage particles for later use (1).
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