The coordination of V-ATPase and ATG16L1 is part of a common mechanism of non-canonical autophagy.

The conjugation of Atg8-family proteins with phospholipids on the double-membrane phagophore is one of the hallmarks of macroautopahgy/autophagy. However, in the past decades, Atg8-family proteins have also been identified on single-membrane structures, including the phagosome, endosome and lysosome. While the physiological importance of the non-canonical Atg8-family protein conjugation has been demonstrated, the mechanism of this process and the underlying regulation are still not very clear. In a recent paper, Hooper et al. found that during LC3-associated phagocytosis, reactive oxygen species are required for V-ATPase assembly, which is essential for the subsequent LC3 conjugation to the phagosome. Enhanced V-ATPase assembly and the direct engagement of ATG16L1 are also observed in a wide range of non-canonical Atg8-family protein conjugation processes, defining the V-ATPase and ATG16L1 as taking part in a common mechanism.