Recent data both from cell-free experiments and from cultured cells have sh
own that lysosomes can fuse directly with late endosomes to form a hybrid o
rganelle. This has a led to a hypothesis that dense core lysosomes are in e
ssence storage granules for acid hydrolases and that, when the former fuse
with late endosomes, a hybrid organelle for digestion of endocytosed macrom
olecules is created. Lysosomes are then re-formed from hybrid organelles by
a process involving condensation of contents. In this Commentary we review
the evidence for formation of the hybrid organelles and discuss the curren
t status of our understanding of the mechanisms of fusion and lysosome re-f
ormation. We also review lysosome biosynthesis, showing how recent studies
of lysosome-like organelles including the yeast vacuole, Drosophila eye pig
ment granules and mammalian secretory lysosomes have identified novel prote
ins involved in this process.