Hungry cells sometimes digest a portion of their contents inside structures called autophagosomes. Razi et al. identify a key step in autophagosome maturation, showing that it depends on early stages in the endocytic pathway that enables cells to absorb necessities from their surroundings.
An autophagosome is like a miniature stomach that uses enzymes to dissolve macromolecules and organelles. The process of self-eating, known as autophagy, recaptures macromolecules and clears away potentially toxic protein tangles. But before an autophagosome can start digesting, it has to combine with endosomes and lysosomes that provide the necessary enzymes. Researchers knew that maturing autophagosomes fuse with late endosomes, which are far along in the endocytic pathway and break down absorbed material. But they didn't know whether the youthful autophagosomes also merge with early endosomes that harbor freshly imbibed molecules.
To find out, Razi et al. deleted components of the coatomer complex COPI, which is necessary for endosome function. Loss of COPI disrupted early endosomes, reducing absorption and processing of two molecules taken in via the endocytic pathway. COPI's absence also gave cells indigestion: immature, nonfunctional autophagosomes built up in the cells.
The results suggest that to start working, an autophagosome has to fuse not just with late endosomes, but also with early endosomes. What the autophagosome gains from the rendezvous is a question for future studies. But the researchers suspect that early endosomes provide the molecular pump that helps acidify the autophagosome's interior.
