Autophagy regulation through Atg9 traffic

Abstract

Rapid membrane expansion is the key to autophagosome formation during nutrient starvation. In this issue, Yamamoto et al. (2012. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201202061) now provide a mechanism for vesicle-mediated initiation of autophagosome biogenesis. They show that Atg9 vesicles, produced de novo during starvation, are ∼30-60 nm in size and contain ∼30 molecules of Atg9. These vesicles assemble to form an autophagosome, and subsequently, the Atg9 embedded in the outer membrane is recycled to avoid degradation.

Figure 1.

Trafficking routes of Atg9. Red carriers indicate vesicles delivering Atg9 to autophagosomal intermediates (anterograde transport; continuous arrows). The vesicles involved in the retrieval of Atg9 from the autophagosomal membranes are shown in blue (retrograde transport; dashed arrows). Note that for clarity, the Atg9 present in the Golgi complex, the Atg9 reservoirs, or the endosomes is not depicted in either A or B. (A) In yeast, Atg9 is transported from the Golgi to the PAS and/or early autophagosomal precursors in small, highly motile vesicles described by Yamamoto et al. (2012) and then retrieved from complete autophagosomes and/or vacuole membranes (black arrows). Gray arrows indicate possible transport routes of Atg9 from and to the Atg9 reservoirs and/or the CUPSs (involved in unconventional secretion of Acb1; Bruns et al., 2011). (B) In mammals, mAtg9 trafficked between the Golgi and endosomes in the presence of nutrients. mAtg9 is also found in reservoir-like structures close to Golgi and endosomes. Upon autophagy induction, mAtg9 distributes to endosomal compartments, although the pool at the Golgi (continuous black arrows) or in reservoir-like structures (continuous gray arrows) appears to play a more significant part in autophagosome biogenesis. Contributions from endosomes, however, cannot be excluded. mAtg9 dynamically associates with autophagosomal precursors and undergoes continuous cycling, but it remains unclear whether it is retrieved back to the Golgi (dashed black arrows) or endosomes (dashed gray arrows). Because mAtg9 is not detected on the autophagosome, amphisome, and lysosome surface, mAtg9 removal from the autophagosomal membrane is probably completed before the autophagosome is closed or completed.