RRC ID 45890
Author Xu S, Chisholm AD.
Title C. elegans epidermal wounding induces a mitochondrial ROS burst that promotes wound repair.
Journal Dev Cell
Abstract Reactive oxygen species (ROS) such as hydrogen peroxide are generated at wound sites and act as long-range signals in wound healing. The roles of other ROS in wound repair are little explored. Here, we reveal a cytoprotective role for mitochondrial ROS (mtROS) in Caenorhabditis elegans skin wound healing. We show that skin wounding causes local production of mtROS superoxide at the wound site. Inhibition of mtROS levels by mitochondrial superoxide-specific antioxidants blocks actin-based wound closure, whereas elevation of mtROS promotes wound closure and enhances survival of mutant animals defective in wound healing. mtROS act downstream of wound-triggered Ca(2+) influx. We find that the mitochondrial calcium uniporter MCU-1 is essential for rapid mitochondrial Ca(2+) uptake and mtROS production after wounding. mtROS can promote wound closure by local inhibition of Rho GTPase activity via a redox-sensitive motif. These findings delineate a pathway acting via mtROS that promotes cytoskeletal responses in wound healing.
Volume 31(1)
Pages 48-60
Published 2014-10-13
DOI 10.1016/j.devcel.2014.08.002
PII S1534-5807(14)00512-7
PMID 25313960
PMC PMC4197410
MeSH Actins / metabolism Animals Antioxidants / pharmacology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Calcium / metabolism Epidermis / drug effects Epidermis / metabolism* Epidermis / physiology Mitochondria / metabolism* Mitochondrial Membrane Transport Proteins / genetics Mitochondrial Membrane Transport Proteins / metabolism* Reactive Oxygen Species / metabolism* Wound Healing* rho GTP-Binding Proteins / genetics rho GTP-Binding Proteins / metabolism
IF 10.092
Times Cited 80
C.elegans tm1463 tm776 tm760 tm1146 tm3036