Endomembrane damage sensing by V-ATPase recruits ATG16L1 for LC3 lipidation in situ

Yue Xu; Jingjin Ding

doi:10.1080/15548627.2022.2062889

Endomembrane damage sensing by V-ATPase recruits ATG16L1 for LC3 lipidation in situ

Autophagy. 2022 Nov;18(11):2751-2753. doi: 10.1080/15548627.2022.2062889. Epub 2022 Apr 12.

Authors

Yue Xu¹, Jingjin Ding²

Affiliations

¹ Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

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 ATP6V0C^Q124A mutation, illustrating that disruption of the proton gradient in acidic compartments is a universal signal that triggers V-ATPase-ATG16L1-induced LC3 lipidation.

Keywords: ARF; ATG16L1; SopF; V-ATPase; VAIL; endomembrane damage; pH disturbance; selective autophagy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases*
Autophagy
Autophagy-Related Proteins / metabolism
Macroautophagy
Microtubule-Associated Proteins* / metabolism

Substances

Autophagy-Related Proteins
Adenosine Triphosphatases
Microtubule-Associated Proteins

Grants and funding

This research was supported by CAS Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29020202), Excellent Young Scholar Program (81922043) and a General Program (32170749) of the National Natural Science Foundation of China, National Key Research and Development Program of China (2017YFA0504000), and a grant from the Youth Innovation Promotion Association CAS.