线粒体分裂
线粒体
细胞生物学
碎片(计算)
细胞凋亡
化学
信号转导
激活剂(遗传学)
DNA断裂
激酶
活性氧
生物
程序性细胞死亡
生物化学
受体
生态学
作者
Zhuofan Liu,Kuan Liu,Zhiqi Liu,Cong Lin,Meng‐Yu Lei,Jing Li,Zhuo Ma,Yu Deng,Wei Liu,Bin Xu
标识
DOI:10.1016/j.scitotenv.2022.157134
摘要
Manganese (Mn) toxicity is mainly caused by excessive Mn content in drinking water and occupational exposure. Moreover, overexposure to Mn can impair mental, cognitive, memory, and motor capacities. Although melatonin (Mel) can protect against Mn-induced neuronal damage and mitochondrial fragmentation, the underlying mechanism remains elusive. Here, we examined the related molecular mechanisms underlying Mel attenuating Mn-induced mitochondrial fragmentation through the mammalian sterile 20-like kinase-1 (Mst1)/JNK signaling path. To test the role of Mst1 in mitochondrial fragmentation, we treated mouse primary neurons overexpressing Mst1 with Mel and Mn stimulation. In normal neurons, 10 μM Mel reduced the effects of Mn (200 μM) on Mst1 expression at the mRNA and protein levels and on phosphorylation of JNK and Drp1, Drp1 mitochondrial translocation, and mitochondrial fragmentation. Conversely, overexpression of Mst1 hindered the protective effect of Mel (10 μM) against Mn-induced mitochondrial fragmentation. Anisomycin (ANI), an activator of JNK signaling, was similarly found to inhibit the protective effect of Mel on mitochondria, while Mst1 levels were not significantly changed. Thus, our results demonstrated that 10 μM Mel negatively regulated the Mst1-JNK pathway, thereby reducing excessive mitochondrial fission, maintaining the mitochondrial network, and alleviating Mn-induced mitochondrial dysfunction.
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