Zhang Liting, Zhang Chuchu, Zhang Junjie
Changzhou Wujin People's Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou 213002, Jiangsu, China.
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, State Key Laboratory of Virology and Biosafety, Medical Research Institute, Wuhan University, Wuhan 430071, Hubei, China.
Cell Insight. 2025 Jul 24;4(5):100266. doi: 10.1016/j.cellin.2025.100266. eCollection 2025 Oct.
Mediator of IRF3 activation (MITA)/Stimulator of Interferon Genes (STING) (also known as MPYS/ERIS) is a crucial adaptor protein for initiating antiviral innate immune responses to intracellular DNA and DNA viruses. MITA binds cGAMP, a second messenger synthesized by cGAS in response to intracellular DNA, culminating in the induction of type I interferons (IFNs), inflammatory cytokines, and interferon-stimulated genes (ISGs). While the canonical IFN-dependent MITA signaling has been extensively studied, recent research has unveiled a growing repertoire of IFN-independent functions of MITA in various physiological processes and pathological conditions. These non-canonical roles of MITA are increasingly recognized for their involvement in critical processes such as antiviral activity, senescence, autophagy, metabolism, lysosomal biogenesis, and the development of neurological disorders. In this review, we summarize the latest advances in understanding MITA's non-canonical functions and provide insights into key scientific questions that remain to be addressed. Deciphering how MITA is involved in these complex physiological and pathological processes will not only deepen our understanding of MITA signaling, but may also offer new therapeutic targets for treating related diseases.
干扰素调节因子3激活介质（MITA）/干扰素基因刺激物（STING）（也称为MPYS/ERIS）是启动针对细胞内DNA和DNA病毒的抗病毒固有免疫反应的关键衔接蛋白。MITA结合cGAMP，cGAMP是cGAS响应细胞内DNA合成的第二信使，最终导致I型干扰素（IFN）、炎性细胞因子和干扰素刺激基因（ISG）的诱导。虽然经典的依赖IFN的MITA信号通路已被广泛研究，但最近的研究揭示了MITA在各种生理过程和病理状况下越来越多不依赖IFN的功能。MITA的这些非经典作用因其参与抗病毒活性、衰老、自噬、代谢、溶酶体生物发生和神经疾病发展等关键过程而日益受到认可。在本综述中，我们总结了在理解MITA非经典功能方面的最新进展，并对仍有待解决的关键科学问题提供见解。阐明MITA如何参与这些复杂的生理和病理过程不仅将加深我们对MITA信号通路的理解，还可能为治疗相关疾病提供新的治疗靶点。
