THE ROLE OF INTRACELLULAR CHOLESTEROL TRANSPORT IN CHOLESTEROL HOMEOSTASIS

How cholesterol is transported among the membranes of the cell is obsc ure. Similarly, the mechanisms governing the abundance of cell cholest erol are not entirely understood. It may be, however, that a link exis ts between ate intracellular transport of cholesterol and its homeosta sis. We propose that cholesterol circulates between the plasma membran e, which contains the bulk of the sterol, and organelle membranes, whi ch contain only traces. A putative sensor translates small fluctuation s in plasma membrane cholesterol into relatively large changes in this flux, thereby setting the magnitude of the intracellular pools. The c holesterol concentration in the endoplasmic reticulum and mitochondria l membranes then governs the activities of proteins embedded therein t hat mediate cholesterol transformations. This arrangement creates a fe edback loop through which the intracellular effecters regulate the abu ndance of plasma membrane cholesterol.