RRC ID 59491
Author Fu H, Zhou H, Yu X, Xu J, Zhou J, Meng X, Zhao J, Zhou Y, Chisholm AD, Xu S.
Title Wounding triggers MIRO-1 dependent mitochondrial fragmentation that accelerates epidermal wound closure through oxidative signaling.
Journal Nat Commun
Abstract 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.
Volume 11(1)
Pages 1050
Published 2020-2-26
DOI 10.1038/s41467-020-14885-x
PII 10.1038/s41467-020-14885-x
PMID 32103012
PMC PMC7044169
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Calcium / metabolism Cytochrome P-450 Enzyme System / metabolism GTP Phosphohydrolases / genetics Mitochondria / metabolism Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism* Oxidation-Reduction Oxidative Stress / physiology Reactive Oxygen Species / metabolism Wound Healing / physiology* rho GTP-Binding Proteins / genetics rho GTP-Binding Proteins / metabolism*
IF 11.878
C.elegans tm1108 tm1133 tm1107 tm1966 tm2143