The Role of ATG9 Vesicles in Autophagosome Biogenesis

Autophagy mediates the degradation and recycling of cellular material in the lysosomal system. Dysfunctional autophagy is associated with a plethora of diseases including uncontrolled infections, cancer and neurodegeneration. In macroautophagy (hereafter autophagy) this material is encapsulated in double membrane vesicles, the autophagosomes, which form upon induction of autophagy. The precursors to autophagosomes, referred to as phagophores, first appear as small flattened membrane cisternae, which gradually enclose the cargo material as they grow. The assembly of phagophores during autophagy initiation has been a major subject of investigation over the past decades. A special focus has been ATG9, the only conserved transmembrane protein among the core machinery. The majority of ATG9 localizes to small Golgi-derived vesicles. Here we review the recent advances and breakthroughs regarding our understanding of how ATG9 and the vesicles it resides in serve to assemble the autophagy machinery and to establish membrane contact sites for autophagosome biogenesis. We also highlight open questions in the field that need to be addressed in the years to come.