14.6 Directing Membrane Proteins and Cytosolic Materials to the Lysosome

The major function of lysosomes is to degrade extracellular materials taken up by the cell and to degrade intracellular components under certain conditions. Materials to be degraded must be delivered to the lumen of the lysosome, where the various degradative enzymes reside. As we have just seen, endocytosed ligands (e.g., LDL particles) that dissociate from their receptors in the late endosome subsequently enter the lysosomal lumen when the membrane of the late endosome fuses with the membrane of the lysosome (see Figure 14-29). Likewise, phagosomes carrying bacteria or other particulate matter can fuse with lysosomes, releasing their contents into the lumen for degradation.

It is apparent how the general vesicular trafficking mechanism discussed in this chapter can be used to deliver the luminal contents of an endosomal organelle to the lumen of the lysosome for degradation. However, membrane proteins delivered to the lysosome by the typical vesicular trafficking process we have discussed in this chapter should ultimately be delivered to the membrane of the lysosome. How, then, are membrane proteins delivered to the interior of the lysosome for degradation? As we will see in this section, the cell has two different specialized pathways for delivery of materials to the lysosomal lumen for degradation, one for membrane proteins and one for cytosolic materials. The first pathway, used to degrade endocytosed membrane proteins, uses an unusual type of vesicle that buds into the lumen of the endosome to produce a multivesicular endosome. The second pathway, known as autophagy, involves the de novo formation of a double-membrane organelle known as an autophagosome that envelops cytosolic material, such as soluble cytosolic proteins, or sometimes organelles, such as peroxisomes or mitochondria. Both pathways lead to fusion of either the multivesicular endosome or autophagosome with the lysosome, depositing the contents of these organelles into the lysosomal lumen for degradation.