Wang Xiaoding, Zhang Guangyu
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China.
Ageing Res Rev. 2025 Jan;103:102603. doi: 10.1016/j.arr.2024.102603. Epub 2024 Nov 26.
The ISR is a cellular signaling pathway that responds to various physiological changes and types of stimulation. The mitochondrial integrated stress response (ISR) is a stress response specific to mitochondria which is initiated by eIF2α phosphorylation and is responsive to mitochondrial stressors. The ISR triggers diverse metabolic responses reliant on activating transcription factor 4 (ATF4). The preliminary phases of ISR can provoke an adaptive stress response that antagonizes age-related diseases and promotes longevity. In this review, we provide an overview of the molecular mechanisms of the ISR, with a particular focus on its potential as a therapeutic target for age-related disease and the promotion of longevity.
综合应激反应(ISR)是一种细胞信号通路,可对各种生理变化和刺激类型做出反应。线粒体综合应激反应(ISR)是一种特定于线粒体的应激反应,由真核起始因子2α(eIF2α)磷酸化引发,并对线粒体应激源做出反应。ISR通过激活转录因子4(ATF4)触发多种代谢反应。ISR的初始阶段可引发适应性应激反应,对抗与年龄相关的疾病并促进长寿。在本综述中,我们概述了ISR的分子机制,特别关注其作为与年龄相关疾病的治疗靶点和促进长寿的潜力。