Cellular catabolism of triglyceride-rich lipoproteins

The intravascular metabolism of lipoproteins has been quite extensively studied, however, the intracellular destiny of lipoproteins other than low-density lipoproteins (LDLs) has not yet been further elucidated. We studied the intracellular fate of triglyceride-rich lipoproteins (TRL) associated with lipoprotein lipase (LpL) in human hepatoma cells and fibroblasts. By pulse chase experiments, it was demonstrated that apolipoprotein E (apoE), other surface apolipoproteins and LpL escape lysosomal hydrolysis and are released intact into the medium, whereas apolipoprotein B (apoB) and other high molecular weight proteins are degraded. Kinetic studies revealed that recycling apolipoproteins are retained inside the cell much longer than transferrin (Tf), a well-established marker for the recycling pathway, is. The intracellular pathway of TRL was further investigated using indirect immunofluorescence for apoE, LpL and lipids. In contrast to fluorescence-labeled lipids, which are delivered to lysosomal compartments, apoE and LpL follow a distinct route to a sorting compartment, clearly distinguishable from the well-established perinuclear Tf recycling compartment. The surface apoproteins remain therefore accessible for slow recycling back to the plasma membrane, and possible reintegration into lipoproteins.