摘要：SummaryThe mitochondrial unfolded protein response (UPRmt) is an organellar stress signaling pathway that functions to detect and restore disruption of mitochondrial proteostasis. The UPRmtis 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 UPRmtis integral to zebrafish fin regeneration. Taking advantage of a novel zebrafish UPRmtreporter, we observed that UPRmtactivation occurs in regenerating fin tissue shortly after injury. Through chemical and genetic approaches, we discovered that the Sirt1-UPRmtpathway, 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 UPRmtactivation and promotes tissue regeneration.Graphical abstractDisplay OmittedHighlights•The mitochondrial unfolded protein response is activated during fin regeneration•The pathway, requiring NAD+, is stimulated in both injured larval and adult fins•The sirtuin (Sirt1) pathway is also activated and required for regeneration•Sirtuin promotes mitochondrial biogenesis due to increased NAD+ in the blastemaMolecular biology; Cell biology; Developmental biology
