Intracellular degradation of asialoglycoproteins in hepatocytes starts in a subgroup of lysosomes

Isolated rat hepatocytes take up and degrade 125I]tyramine-cellobiose-labelled asialofetuin ( 125I]TC-AF). The labelled degradation products are trapped at the site of degradation. The intracellular transport of 125I]TC-AF was studied by means of cell fractionation in Nycodenz gradients. The labelled ligand was kept in a small, slowly sedimenting vesicle during the first minutes after uptake in the cells, and was then transferred to a larger endosome. Labelled degradation products first appeared in an organelle with the same density distribution as the larger endosome and then in a denser organelle. These observations suggest that two types of lysosome, 'light' lysosomes and 'dense', are sequentially involved in the degradation of the asialoglycoprotein. The bulk of the lysosomal enzymes is associated with the dense lysosome.