title: C. elegans epidermal wounding induces a mitochondrial ROS burst that promotes wound repair.
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.
authors.affiliation: Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Suhong
authors.initials: S
authors.lastname: Xu
authors.affiliation: Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. Electronic address: chisholm@ucsd.edu.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Chisholm
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014945:Wound Healing; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D000975:Antioxidants; D029742:Caenorhabditis elegans Proteins; C000594125:Mcu-1 protein, C elegans; D033681:Mitochondrial Membrane Transport Proteins; D017382:Reactive Oxygen Species; C560609:RHO-1 protein, C elegans; D020741:rho GTP-Binding Proteins; D002118:Calcium