Cellular homeostasis is intricately influenced by stimuli from the microenvironment, including signaling molecules, metabolites, and pathogens. Functioning as a signaling hub within the cell, mitochondria integrate information from various intracellular compartments to regulate cellular signaling and metabolism. Multiple studies have shown that mitochondria may respond to various extracellular signaling events. However, it is less clear how changes in the extracellular matrix (ECM) can impact mitochondrial homeostasis to regulate animal physiology. We find that ECM remodeling alters mitochondrial homeostasis in an evolutionarily conserved manner. Mechanistically, ECM remodeling triggers a TGF-β response to induce mitochondrial fission and the unfolded protein response of the mitochondria (UPR^MT). At the organismal level, ECM remodeling promotes defense of animals against pathogens through enhanced mitochondrial stress responses. We postulate that this ECM-mitochondria crosstalk represents an ancient immune pathway, which detects infection- or mechanical-stress-induced ECM damage, thereby initiating adaptive mitochondria-based immune and metabolic responses.

细胞稳态受到微环境刺激的复杂影响，包括信号分子、代谢物和病原体。线粒体作为细胞内的信号中枢，整合来自各个细胞内区室的信息来调节细胞信号和代谢。多项研究表明线粒体可能对各种细胞外信号事件做出反应。然而，细胞外基质（ECM）的变化如何影响线粒体稳态以调节动物生理机能尚不清楚。我们发现 ECM 重塑以进化保守的方式改变线粒体稳态。从机制上讲，ECM 重塑触发 TGF-β 反应，诱导线粒体裂变和线粒体的未折叠蛋白反应 (UPR ^MT )。在有机体水平上，ECM 重塑通过增强线粒体应激反应促进动物抵御病原体。我们假设这种 ECM-线粒体串扰代表了一种古老的免疫途径，它可以检测感染或机械应力诱导的 ECM 损伤，从而启动基于线粒体的适应性免疫和代谢反应。