<i>Dusp1</i> regulates thermal tolerance limits in zebrafish by maintaining mitochondrial integrity

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 dusp1-/- 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.物种对于温度的耐受程度限制了它们的分布范围。然而，确定生物体温度耐受极限的分子和细胞机制尚不清楚。该文报道了双特异性丝氨酸磷酸酶1 ( dusp1)在温度耐受调节中的重要作用。 Dusp1-/- 缺失的突变体斑马鱼生长正常，但其生存的温度范围缩小。通过研究我们发现，突变体斑马鱼对冷和热的耐受程度通常归因于线粒体功能障碍的加剧和鳃中产生过多的活性氧加速了细胞死亡的进程。DUSP1-MAPK-DRP1轴被认为是调节鱼类和人类细胞中这些过程的关键通路。这些研究结果表明DUSP1在维持线粒体完整性和氧化还原稳态中发挥了重要作用。我们认为维持细胞氧化还原稳态可能是细胞应对温度应激的关键机制，而调节温度最敏感的组织(即鳃)中氧化还原稳态的信号通路之间的相互作用可能在限定斑马鱼温度耐受极限方面发挥重要作用。.