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.
Autophagy, Endosomes, Homeostasis, Lysosomes, Membrane Proteins
University of Texas Southwestern Medical Center
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