New insight into the role of proteins in autophagosome-vacuole fusion

Similar to endosome–vacuole fusion, the fusion of autophagosomes with vacuoles requires the action of the RAB7-like GTPase Ypt7, the homotypic vacuole fusion and protein sorting (HOPS) tethering complex, and SNARE protein. SNAREs associate on opposing membranes, zipper their SNARE domains, and thereby deform the bilayers, driving lipid rearrangements that lead to membrane fusion. Indeed, it is unclear which SNARE on the yeast autophagosome supports fusion with the vacuole. We established an in vitro reconstitution system for autophagosome–vacuole fusion, which allowed us to identify the molecular players required for fusion as well as their place of action. We discovered that fusion requires the R-SNARE Ykt6 on the autophagosome, together with the Q-SNAREs Vam3, Vam7, and Vti1 on the vacuole. The Kraft lab thus showed that autophagosome–vacuole fusion is though related, distinct to other fusion processes such as vacuole–vacuole or endosome–vacuole fusion.