Intracellular cholesterol transport

Recent data on the roles of vesicle- and 'raft'-mediated pathways in intracellular free cholesterol (FC) transport are reviewed. Cholesterol internalized from plasma lipoproteins is transferred via endocytic vesicles to the trans-Golgi network (TGN), consistent with prior data indicating a key role for this organelle in protein and lipid sorting and transport. Newly synthesized and lipoprotein-derived FC are returned to the cell surface by a common raft-dependent pathway. Intracellular FC transport promotes the delivery of GPI-anchored proteins to the cell surface; it is also an additional mechanism to regulate cell FC content. Many peripheral cells express caveolin, an FC-binding protein localized to plasma membrane caveolae. FC delivery to cell surface caveolae is accelerated by caveolin. Caveolar FC becomes targeted to small, lipid-poor (prebeta-) high density lipoprotein particles. Caveolin may protect quiescent cells, regulating FC efflux more efficiently in response to changing medium lipoprotein concentrations. Overall, these recent findings suggest that cell FC content can be regulated at the levels of both influx and efflux, and indicate key roles for the TGN and in cells expressing caveolin, cell-surface caveolae.