cGAS-STING通路调控自噬溶酶体系统的研究进展

Research progress on the regulation of the autophagy-lysosome system by the cGAS-STING pathway

摘要

环状GMP-AMP合成酶-干扰素基因刺激物(cyclic GMP-AMP synthase-stimulator of interferon genes，cGAS-STING)信号通路作为细胞内识别胞质双链DNA的关键先天免疫机制，其经典作用是通过诱导Ⅰ型干扰素及炎症因子的表达来发挥抗病毒免疫功能。然而，近年研究发现该通路中的关键分子不仅转导免疫信号，还存在非经典功能，可以通过多种机制诱导自噬。最新研究揭示，STING还能够驱动由转录因子EB(transcription factor EB，TFEB)介导的溶酶体生物发生。这些发现表明cGAS-STING通路是连接先天免疫与自噬溶酶体系统的关键纽带。该系统的激活会产生多种效应，从维持稳态到加剧疾病进展，具体取决于特定的病理环境。文章旨在综述cGAS-STING通路诱导激活自噬溶酶体系统的分子机制及病理生理作用的最新研究进展，以期为深入理解该通路的生物学功能及相关疾病治疗策略提供参考。

Abstract

The cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)signaling pathway is a pivotal innate immune mechanism for sensing cytosolic double-stranded DNA. Its canonical role is to exert antiviral immunity by inducing the expression of type Ⅰ interferons and pro-inflammatory cytokines. However，recent studies have revealed that key components of this pathway possess non-canonical functions capable of inducing autophagy through diverse mechanisms. Recent studies have revealed that STING can also drive lysosomal biogenesis mediated by transcription factor EB(TFEB). These findings suggest that the cGAS-STING axis serves as a critical bridge linking innate immunity with the autophagy-lysosomal system. The activation of this pathway yields pleiotropic effects，ranging from homeostatic preservation to the aggravation of disease progression，depending on the specific pathological milieu. This review aims to summarize the latest advances in the molecular mechanisms and pathophysiological roles of the cGAS-STING-mediated activation of the autophagy-lysosomal system，providing a comprehensive framework for understanding its biological functions and informing potential therapeutic strategies for related diseases.

关键词

cGAS-STING / 自噬 / 溶酶体生物发生 / 转录因子EB

Key words

cGAS-STING / autophagy / lysosomal biogenesis / transcription factor EB

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基金资助

苏州市科技发展计划项目(SKY2023210)