Wounding triggers MIRO-1 dependent mitochondrial fragmentation that accelerates epidermal wound closure through oxidative signaling
Wounding triggers MIRO-1 dependent mitochondrial fragmentation that accelerates epidermal wound closure through oxidative signaling
复制标题
受伤会触发 MIRO-1 依赖性线粒体断裂，通过氧化信号加速表皮伤口闭合。
DOI：
10.1038/s41467-020-14885-x
复制
发表时间：
2020-02-26
影响因子：
16.6
通讯作者：
Xu, Suhong
中科院分区：
文献类型：
--
作者：
Fu, Hongying;Zhou, Hengda;Xu, Suhong
生物体通过保护性反应的上调来对组织损伤做出反应，所述保护性反应恢复组织结构和代谢功能。线粒体是维持细胞内稳态的细胞内氧化代谢信号的关键来源。在这里，我们报告说，组织和细胞损伤触发快速和可逆的线粒体断裂。fzo-1融合缺陷突变体或急性药物治疗后线粒体碎片的升高加速了肌动蛋白为基础的伤口闭合。创伤引发的线粒体片段化不依赖于GTdR DRP-1，但通过线粒体Rho GTdR MIRO-1和胞质Ca 2+起作用。fzo-1突变体的破碎线粒体和加速伤口闭合依赖于MIRO-1功能。遗传和转录组学分析表明，增强的线粒体片段化通过上调mtROS和细胞色素P450加速伤口闭合。我们的研究结果揭示了线粒体动力学如何响应细胞和组织损伤并促进组织修复。
Organisms respond to tissue damage through the upregulation of protective responses which restore tissue structure and metabolic function. Mitochondria are key sources of intracellular oxidative metabolic signals that maintain cellular homeostasis. Here we report that tissue and cellular wounding triggers rapid and reversible mitochondrial fragmentation. Elevated mitochondrial fragmentation either in fzo-1 fusion-defective mutants or after acute drug treatment accelerates actin-based wound closure. Wounding triggered mitochondrial fragmentation is independent of the GTPase DRP-1 but acts via the mitochondrial Rho GTPase MIRO-1 and cytosolic Ca2+. The fragmented mitochondria and accelerated wound closure of fzo-1 mutants are dependent on MIRO-1 function. Genetic and transcriptomic analyzes show that enhanced mitochondrial fragmentation accelerates wound closure via the upregulation of mtROS and Cytochrome P450. Our results reveal how mitochondrial dynamics respond to cellular and tissue injury and promote tissue repair.