A conserved ion channel function of STING mediates non-canonical autophagy and cell death

ABSTRACT: The cGAS/STING pathway triggers inflammation upon diverse cellular stresses such as infection, cellular damage, aging, and diseases. STING also triggers non-canonical autophagy, involving LC3 lipidation on STING vesicles through the V-ATPase-ATG16L1 axis, as well as induces cell death. Although the proton pump V-ATPase senses organelle de-acidification in other contexts, it is unclear how STING activates V-ATPase for non-canonical autophagy. Here we report a conserved channel function of STING in proton efflux and vesicle de-acidification. STING activation induces an electron-sparse pore in its transmembrane domain, which mediates proton flux in vitro and the de-acidification of post-Golgi STING vesicles in cells. A chemical ligand of STING, C53, which binds to and blocks its channel, stro

SUBMITTER: Jinrui Xun 

PROVIDER: S-SCDT-10_1038-S44319-023-00045-X | biostudies-other |

REPOSITORIES: biostudies-other