During autophagy, intracellular material is degraded or recycled, which is important for cellular homeostasis or organelle clearance after damage or developmental processes. Formation of the double-membrane autophagosomes, which deliver the autophagy targets to the lysosome, depends on highly conserved autophagy-related (Atg) proteins. Atg9A is the only mammalian transmembrane core Atg protein and is found at the trans-Golgi network, the endosomal system and, upon starvation-induced autophagy, transiently at autophagic membranes. Now, Takeshi Noda, Tamotsu Yoshimori and co-workers (p. 3781) report on the significance of trafficking of Atg9A for autophagosome formation. They identify a sorting motif in the cytosolic, N-terminal domain of Atg9A, which interacts with the adaptor protein AP-2. Stable expression of an N-terminal Atg9A truncation mutant in Atg9A-knockout mouse embryonic fibroblasts prevents formation of autophagosomes and impairs starvation-based nonselective autophagy, as well as selective autophagy against Salmonella bacteria. Conversely, an Atg9A variant that lacks the sorting motif loses its Golgi localisation and accumulates at the recycling endosomes. Similarly, the knockdown of the transport protein particle (TRAPP) subunit TRAPPC8, which blocks autophagosome formation, leads to an increase of Atg9A at recycling endosomes. On the basis of these data, the authors propose that trafficking of Atg9A through recycling endosomes is a required step for selective and canonical autophagy.
- © 2016. Published by The Company of Biologists Ltd