A SNARE and specific COPII requirements define ER-derived vesicles for the biogenesis of autophagosomes

Abstract

The endoplasmic reticulum (ER) is a major source for the generation of autophagosomes during macroautophagy. Our recent work in yeast shows that particular ER-derived vesicles are generated for the biogenesis of autophagosomes. These vesicles not only incorporate a SNARE protein that is largely ER-resident under nonstarving conditions, but also display COPII requirements for ER-exit that differ from conventional cargo-transporting vesicles. Our results suggest that specific intracellular traffic is launched at the ER for the transport of membranes to sites of autophagosome formation.

Keywords: COPII; SNARE proteins; autophagy; membrane fusion; membrane traffic.

Figure 1.

Current models for the contribution of ER-derived COPII vesicles to autophagosome biogenesis. (1) Upon cellular starvation, vesicles are produced that differ from conventional transport vesicles in several aspects. Our work suggests that in yeast, such vesicles incorporate the Qa-SNARE Ufe1 and have specific COPII requirements for budding, maybe due to subtle differences in coat arrangement. Likewise in mammals, starvation-specific and unusually small COPII vesicles are produced at the ERGIC. Based on these findings and the assumed functional role of such vesicles it is possible that they constitute a class of ER vesicles that is free of lumenal cargo and carries mainly membranes and fusion machinery instead, but evidence for this assumption is lacking. (2) Previous work with yeast suggests an alternative mechanism for the contribution of COPII vesicles to autophagosome biogenesis. In this scenario, transport vesicles are generated normally, but are diverted from their route to the Golgi and are targeted to sites of autophagosome formation by virtue of a starvation-specific membrane tethering factor. As a consequence, lumenal cargo might end up in between the 2 membranes that form an autophagosome.