EVIDENCE FOR A CHOLESTEROL TRANSPORT PATHWAY FROM LYSOSOMES TO ENDOPLASMIC-RETICULUM THAT IS INDEPENDENT OF THE PLASMA-MEMBRANE

We have studied the movement of low density lipoprotein (LDL)-derived cholesterol in cultured Chinese hamster ovary cells, Our hypothesis is that when LDL cholesterol is effluxed from lysosomes, the bulk of LDL cholesterol is mobilized to the plasma membrane, while another pathwa y delivers LDL cholesterol from lysosomes to acyl-CoA/cholesterol acyl transferase (ACAT) in the endoplasmic reticulum. Three lines of eviden ce support this model, First, LDL cholesterol transport to ACAT can be blocked without inhibiting the movement of cholesterol from lysosomes to plasma membrane or from plasma membrane to endoplasmic reticulum, Second, LDL cholesterol transport to ACAT is normal in a Chinese hamst er ovary mutant with defective plasma membrane-to-ACAT movement, Third , LDL cholesterol is not diluted by the plasma. membrane cholesterol p ool before reaching ACAT, Our evidence supports a vesicular model of c holesterol transport from lysosomes to the endoplasmic reticulum that is independent; of the plasma membrane.