Lin Yi-Fan, Sam Jessica, Evans Todd
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, LC-708, New York, NY 10065, USA.
Institute of Biotechnology, National Tsing Hua University, Hsinchu, 30013, Taiwan.
iScience. 2021 Sep 11;24(10):103118. doi: 10.1016/j.isci.2021.103118. eCollection 2021 Oct 22.
The mitochondrial unfolded protein response (UPR) is an organellar stress signaling pathway that functions to detect and restore disruption of mitochondrial proteostasis. The UPR 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 is integral to zebrafish fin regeneration. Taking advantage of a novel zebrafish UPR reporter, we observed that UPR activation occurs in regenerating fin tissue shortly after injury. Through chemical and genetic approaches, we discovered that the Sirt1-UPR 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 activation and promotes tissue regeneration.
线粒体未折叠蛋白反应（UPR）是一种细胞器应激信号通路，其功能是检测并恢复线粒体蛋白质稳态的破坏。UPR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、神经退行性变和癌症。在此，我们报告UPR对斑马鱼鳍再生至关重要。利用一种新型的斑马鱼UPR报告基因，我们观察到损伤后不久再生鳍组织中就会发生UPR激活。通过化学和遗传学方法，我们发现以促进寿命延长作用而闻名的Sirt1-UPR通路对鳍再生至关重要。在这种情况下，NAD的代谢是Sirt1活性的重要贡献因素。我们提出，Sirt1激活诱导损伤鳍组织中的线粒体生物发生，这导致UPR激活并促进组织再生。
