摘要
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.