articleProceedings of the National Academy of SciencesFeb 21, 2025HYBRID OA

STING-induced noncanonical autophagy regulates endolysosomal homeostasis

The University of Texas Southwestern Medical Center

PubMed
Indexed incrossrefpubmed

Abstract

The cGAS-STING pathway mediates innate immune responses to cytosolic DNA. In addition to its well-established role in inducing inflammatory cytokines, activation of the cGAS-STING pathway also induces noncanonical autophagy, a process involving the conjugation of the ATG8 family of ubiquitin-like proteins to membranes of the endolysosomal system. The mechanisms and functions of STING-induced autophagy remain poorly understood. In this study, we demonstrated that STING activation induced formation of pH-elevated Golgi-derived vesicles that led to ATG16L1 and V-ATPase-dependent noncanonical autophagy. We showed that STING-induced noncanonical autophagy resulted in activation of the MiT/TFE family of…

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