Mechanism and Functions of STING-Induced Noncanonical Autophagy

The cGAS-STING pathway is a vital component of innate immunity. In addition to its well-established role in inducing proinflammatory cytokines, activation of the pathway also induces noncanonical autophagy. Despite an increasing body of research on STING-induced noncanonical autophagy, our understanding of its mechanisms, and particularly its functions, remains limited. In this study, we demonstrated that STING-induced noncanonical autophagy requires the interaction between V-ATPase and the ATG16L1-WD40 domain on Rab7-coated endolysosomal compartments. Additionally, we unveiled that STING-induced noncanonical autophagy leads to the activation of MiT/TFE transcription factors (TFEB, TFE3, and MITF), promoting endolysosomal biogenesis. Furthermore, we showed that STING-induced noncanonical autophagy induces ALIX-meditated ESCRT machinery recruitment to mitigate endolysosomal perturbation. Our study unraveled the multifaceted functions of STING-induced noncanonical autophagy in regulating endolysosomal homeostasis.

Author dc:creator

• Huang, Tuozhi

Contributors dc:contributor

• Liu, Yi
• Chen, Zhijian J.
• Beutler, Bruce
• Cobb, Melanie H.

• Autophagy
• Endosomes
• Homeostasis
• Lysosomes
• Membrane Proteins

Language dc:language

en

Identifier

1596185270

OAI identifier oai:identifier

oai:utswmed-ir.tdl.org:2152.5/10808