Wounding triggers MIRO-1 dependent mitochondrial fragmentation that accelerates epidermal wound closure through oxidative signaling

被引：54
作者：
Fu, Hongying [1 ,2 ]
Zhou, Hengda [1 ,2 ,3 ]
Yu, Xinghai [4 ]
Xu, Jingxiu [1 ,2 ,3 ]
Zhou, Jinghua [1 ,2 ]
Meng, Xinan [1 ,2 ]
Zhao, Jianzhi [1 ,2 ]
Zhou, Yu [4 ]
Chisholm, Andrew D. [5 ]
Xu, Suhong [1 ,2 ,3 ,6 ]
机构：
[1] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Ctr Stem Cell & Regenerat Med, Hangzhou 310058, Peoples R China
[2] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Cardiol, Hangzhou 310058, Peoples R China
[3] Zhejiang Univ Univ Edinburgh Inst, 718 East Haizhou Rd, Haining 314400, Zhejiang, Peoples R China
[4] Wuhan Univ, Sch Life Sci, Dept Syst Biol, Wuhan 430072, Peoples R China
[5] Univ Calif San Diego, Div Biol Sci, Sect Cell & Dev Biol, 9500 Gilman Dr, La Jolla, CA 92093 USA
[6] Zhejiang Univ, Sch Med Hangzhou, Womens Hosp, Hangzhou 310058, Peoples R China
来源：
NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期
基金：
中国国家自然科学基金; 中国博士后科学基金;
关键词：
RHO-GTPASES; FISSION; PROMOTES; CELL; KINASE; FUSION; CYTOCHROME-P450; ACTIVATION; METABOLISM; STABILITY;
D O I：
10.1038/s41467-020-14885-x
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
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页数：13
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