Transfer of Cholesterol to the Mitochondrion

Steroid-synthesizing cells have at least three metabolically active pools of cholesterol: (1) a small, metabolically active pool of free cholesterol; (2) a large storage pool in which cholesterol is stored as cholesterol esters of free fatty acids; and (3) a fixed pool of membrane cholesterol, which is not available for steroid synthe-sis.9 The free cholesterol pool is formed from endogenous conversion of acetate to cholesterol via a complex series of reactions and by hydrolysis of cholesterol esters, including those that are part of the storage pool and those that are constituents of low-density lipoprotein (LDL) and high-density lipoprotein (HDL). After cellular uptake of these lipoproteins, LDL is processed through lysozymes, whereas HDL enters the cy-tosolic pool directly. Dietary cholesterol incorporated into LDL is most commonly used for steroid hormone biosynthesis. Although free cholesterol represents only a small fraction of the total cholesterol pool, this fraction can be increased by cAMP stimulation of cytosolic cholesterol esterase and suppression of acyl-coen-zyme A (CoA) cholesterol acyltransferase.10,11

It has been proposed that during processing of the StAR protein, cholesterol is transferred from the outer to the inner mitochondrial membrane. A hydrophobic core may be formed by a protein complex between the outer and inner mitochondrial membrane, through which cholesterol can pass.8

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