Ma Jin, Son Annie Yujin, Son Youlim, Wang Ping-Yuan, Hwang Paul M
Cardiovascular Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD 20892, USA.
Cardiovascular Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD 20892, USA.
Trends Endocrinol Metab. 2025 Jun 12. doi: 10.1016/j.tem.2025.05.004.
Exercise-induced inflammation is regarded as a response to muscle damage from mechanical stress, but controlled immune signaling can be beneficial by promoting metabolic adaptation which, for example, decreases obesity and lowers the risk of diabetes. In addition to oxidative metabolism, mitochondria play a central role in initiating innate immune signaling. We review recent work that has identified the cGAS-STING-NF-κB signaling pathway, activated by the downregulation of mitochondrial proteins CHCHD4 and TRIAP1, as mediating skeletal muscle adaptation to exercise training as well as potentially promoting cellular resilience to environmental stresses. Notably, CHCHD4 haploinsufficiency prevents obesity in aging mice; therefore, this innate immune signaling pathway could be targeted to achieve some of the health benefits of exercise.
运动诱导的炎症被认为是对机械应力导致的肌肉损伤的一种反应，但可控的免疫信号传导通过促进代谢适应可能是有益的，例如，可减少肥胖并降低糖尿病风险。除了氧化代谢外，线粒体在启动先天性免疫信号传导中起核心作用。我们回顾了最近的研究工作，这些研究确定了由线粒体蛋白CHCHD4和TRIAP1下调激活的cGAS-STING-NF-κB信号通路，该通路介导骨骼肌对运动训练的适应，并可能促进细胞对环境压力的恢复力。值得注意的是，CHCHD4单倍体不足可预防衰老小鼠肥胖；因此，这条先天性免疫信号通路可能是实现运动对健康有益作用的靶点。
