Relationship between endosomes and lysosomes

Delivery of endocytosed macromolecules to lysosomes occurs by means of dire ct fusion of late endosomes with lysosomes. This has been formally demonstr ated in a cell-free content mixing assay using late endosomes and lysosomes from rat liver. There is evidence from electron microscopy Studies that th e same process occurs in intact cells. The fusion process results in the fo rmation of hybrid organelles from which lysosomes are reformed. The discove ry of the hybrid organelle has opened up three areas of investigation: (i) the mechanism of direct fusion of late endosomes and lysosomes, (ii) the me chanism of re-formation of lysosomes from the hybrid organelle, and (iii) t he function of the hybrid organelle. Fusion has analogies with homotypic va cuole fusion in yeast. It requires syntaxin 7 as part of the functional tra ns-SNARE [SNAP receptor, where SNAP is soluble N-ethylmaleimide-sensitive f actor (NSF) attachment protein] complex and the release of lumenal calcium to achieve membrane fusion. Reformation of lysosomes from the hybrid organe lle occurs by a maturation process involving condensation of lumenal conten t and probably removal of some membrane proteins by vesicular traffic. Lyso somes may thus be regarded as a type of secretory granule, storing acid hyd rolases in between fusion events with late endosomes. The hybrid organelle is predicted to function as a 'cell stomach', acting as a major site of hyd rolysis of endocytosed macromolecules.