C. elegans Epidermal Wounding Induces a Mitochondrial ROS Burst that Promotes Wound Repair

• Skin wounding triggers local production of the mitochondrial ROS (mtROS) superoxide
• mtROS promotes actin-mediated wound repair
• Mitochondrial Ca2+ uptake is required for mtROS induction and wound repair
• mtROS regulate Rho activity at wound sites via a RHO-1 redox-sensitive motif

SummaryReactive 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 Ca2+ influx. We find that the mitochondrial calcium uniporter MCU-1 is essential for rapid mitochondrial Ca2+ 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.

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