FIGURE 2.

The lysosome is the terminal compartment for endocytosis, phagocytosis, and autophagy. (A) During endocytosis, plasma membrane invaginates to form endocytic vesicles that contain extracellular fluid and membrane cargo. Endocytic vesicles then fuse with early endosomes, which sort cargo for recycling back to the plasma membrane or degradation towards lysosomes. Concurrent with sorting, early endosomes mature into multivesicular bodies that then become late endosomes. Late endosomes also receive newly synthesized cargo including lysosomal proteases. Late endosomes then fuse with terminal lysosomes, which are non-acidic stores of hydrolytic enzymes to form a hybrid endolysosome, where degradation ensues. Endolysosomes may be able to reform terminal lysosomes. Blue arrows indicate recycling/reformation pathways. (B) In phagocytosis, extracellular particles like bacteria are engulfed by the plasma membrane and sequestered within a phagosome. Phagosomes are then thought to mature by sequentially fusing with early and late endosomes, and ultimately lysosomes. This transforms the nascent phagosome from an innocuous organelle into an acidic and degradative phagolysosome, where the particle is digested. The ultimate fate of the phagolysosome is enigmatic. As such, the endo-lysosomal pathway is a template for phagosome maturation. (C) In autophagy, cytoplasmic material like damaged or surplus organelles is targeted for entrapment by the phagophore, a double-bilayer membrane derived from the ER, forming the autophagosome. Akin to phagosomes, autophagosomes also experience a maturation process, ultimately fusing with lysosomes. Upon degradation of cargo, autolysosomes undergo autophagic lysosome reformation, whereby tubular membrane extrusions extrude proto-lysosomes that reform lysosomes consumed during autophagy.