Endomembrane damage sensing by V-ATPase recruits ATG16L1 for LC3 lipidation in situ
Yue Xu &Jingjin Ding
Abstract
LC3 lipidation-mediated selective macroautophagy/autophagy helps eukaryotes to defend against endogenous dangers and foreign invaders. However, LC3 activation mechanisms of selective autophagy are still elusive. We previously determined that the V-ATPase-ATG16L1 axis is critical for LC3 recruitment to bacteria-residing vacuoles, whereas the Salmonella effector SopF directly targets V-ATPase to disrupt ATG16L1 interaction. Here we show that host ARF GTPase binding causes SopF-dependent ADP-ribosylation of the Gln124 site of the ATP6V0C/V0C subunit of V-ATPase. Furthermore, LC3 activation by pH perturbation of endolysosomes and the Golgi apparatus is also abolished by SopF or a ATP6V0CQ124A mutation, illustrating that disruption of the proton gradient in acidic compartments is a universal signal that triggers V-ATPase-ATG16L1-induced LC3 lipidation.
附件下载：
Endomembrane damage sensing by V-ATPase recruits ATG16L1 for LC3 lipidation in situ, Autophagy, 12 Apr 2022
Autophagy, 12 April, 2022, DOI：https://doi.org/10.1080/15548627.2022.2062889
Endomembrane damage sensing by V-ATPase recruits ATG16L1 for LC3 lipidation in situ
Yue Xu &Jingjin Ding
Abstract
LC3 lipidation-mediated selective macroautophagy/autophagy helps eukaryotes to defend against endogenous dangers and foreign invaders. However, LC3 activation mechanisms of selective autophagy are still elusive. We previously determined that the V-ATPase-ATG16L1 axis is critical for LC3 recruitment to bacteria-residing vacuoles, whereas the Salmonella effector SopF directly targets V-ATPase to disrupt ATG16L1 interaction. Here we show that host ARF GTPase binding causes SopF-dependent ADP-ribosylation of the Gln124 site of the ATP6V0C/V0C subunit of V-ATPase. Furthermore, LC3 activation by pH perturbation of endolysosomes and the Golgi apparatus is also abolished by SopF or a ATP6V0CQ124A mutation, illustrating that disruption of the proton gradient in acidic compartments is a universal signal that triggers V-ATPase-ATG16L1-induced LC3 lipidation.
文章链接：https://www.tandfonline.com/doi/full/10.1080/15548627.2022.2062889