The mitochondrial unfolded protein response (UPR^mt) is an organellar stress signaling pathway that functions to detect and restore disruption of mitochondrial proteostasis. The UPR^mt is involved in a wide range of physiological and disease conditions, including aging, stem cell maintenance, innate immunity, neurodegeneration, and cancer. Here we report that the UPR^mt is integral to zebrafish fin regeneration. Taking advantage of a novel zebrafish UPR^mt reporter, we observed that UPR^mt activation occurs in regenerating fin tissue shortly after injury. Through chemical and genetic approaches, we discovered that the Sirt1-UPR^mt pathway, best known for its role in promoting lifespan extension, is crucial for fin regeneration. The metabolism of NAD⁺ is an important contributor to Sirt1 activity in this context. We propose that Sirt1 activation induces mitochondrial biogenesis in injured fin tissue, which leads to UPR^mt activation and promotes tissue regeneration.

线粒体未折叠蛋白反应 (UPR ^mt ) 是一种细胞器应激信号通路，其功能是检测和恢复线粒体蛋白质稳态的破坏。UPR ^mt涉及广泛的生理和疾病状况，包括衰老、干细胞维持、先天免疫、神经变性和癌症。在这里，我们报告 UPR ^mt是斑马鱼鳍再生不可或缺的一部分。利用新型斑马鱼 UPR ^mt报告^基因，我们观察到 UPR ^mt激活发生在受伤后不久的鳍组织再生中。通过化学和遗传方法，我们发现 Sirt1-UPR ^mt通路以其在促进寿命延长方面的作用而闻名，对鳍再生至关重要。在这种情况下，NAD ⁺的代谢是 Sirt1 活性的重要贡献者。我们提出 Sirt1 激活诱导受损鳍组织中的线粒体生物发生，从而导致 UPR ^mt激活并促进组织再生。