<i>Dusp1</i> regulates thermal tolerance limits in zebrafish by maintaining mitochondrial integrity
Ying Wang, 上海海洋大学海洋生物科学国际联合研究中心, 上海 200120, 中国, Huamin Wang, Yan Zhou, Ling-Hong Hu, Jing-Ming Wan, Jihui Yang, Hongbo Niu, Xiu-Ping Hong, Peng Hu, Liangbiao Chen, 上海海洋大学水产种质资源发掘与利用教育部重点实验室, 上海 200120, 中国, 上海海洋大学水产动物遗传育种中心上海市协同创新中心, 上海 200120, 中国
Abstract
Temperature tolerance restricts the distribution of a species. However, the molecular and cellular mechanisms that set the thermal tolerance limits of an organism are poorly understood. Here, we report on the function of dual-specificity phosphatase 1 (DUSP1) in thermal tolerance regulation. Notably, we found that <i>dusp1</i><sup>-/-</sup> zebrafish grew normally but survived within a narrowed temperature range. The higher susceptibility of these mutant fish to both cold and heat challenges was attributed to accelerated cell death caused by aggravated mitochondrial dysfunction and over-production of reactive oxygen species in the gills. The DUSP1-MAPK-DRP1 axis was identified as a key pathway regulating these processes in both fish and human cells. These observations suggest that DUSP1 may play a role in maintaining mitochondrial integrity and redox homeostasis. We therefore propose that maintenance of cellular redox homeostasis may be a key mechanism for coping with cellular thermal stress and that the interplay between signaling pathways regulating redox homeostasis in the most thermosensitive tissue (i.e., gills) may play an important role in setting the thermal tolerance limit of zebrafish.