Mechanism and Functions of STING-Induced Noncanonical Autophagy
type: CreativeWork
description: 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.
abstract: 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: Huang, Tuozhi
language: en
keywords: Autophagy, Endosomes, Homeostasis, Lysosomes, Membrane Proteins
date published: 2026-06-15T19:42:39Z
date modified: 2026-07-24T05:52:36Z
provider: University of Texas Southwestern Medical Center
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Texas Southwestern Medical Center

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2152.5/10808