Editors' ChoiceWOUND REPAIR

New connections: Healed by ROS

See allHide authors and affiliations

Sci. Signal.  27 Mar 2018:
Vol. 11, Issue 523, eaat1605
DOI: 10.1126/scisignal.aat1605

ROS generated by Nox2 or mitochondria play critical roles in mammalian tissue repair pathways.

Unrestrained oxidative stress damages cells and tissues, but the localized production of reactive oxygen species (ROS) participates in wound healing responses in model organisms. Two papers illustrate the critical role of ROS generated by the Nox2 (NADPH oxidase 2) complex or mitochondria in mammalian tissue repair pathways. In the first paper, Hervera et al. (see also Krämer-Albers) investigated how peripheral nerve axotomy in mice enhances neurite outgrowth from the dorsal root ganglia (DRG) after a subsequent spinal cord injury. After sciatic nerve axotomy, macrophages released Nox2-containing exosomes that were taken up by DRGs. These exosomes were transported to the cell body, resulting in the oxidation and inactivation of phosphatase and tensin homolog, stimulation of PI3K/Akt signaling, and DRG outgrowth. Application of the antioxidant NAC to the sciatic nerve limited DRG outgrowth after spinal cord injury. In the second paper, Horn et al. (see also Cooper) investigated how cells repair mechanically induced plasma membrane damage before extracellular Ca2+ influx reaches levels that trigger cell death. In mouse muscle cells and human nonmuscle cells, Ca2+ uptake by mitochondria initiated ROS generation, which activated actin polymerization and wound closure. Quenching mitochondrially produced ROS in mouse muscle exercised ex vivo resulted in greater damage to myofibers and reduced muscle force. Both papers show that globally quenching ROS generation with antioxidants, which are a popular nutritional supplement, may have detrimental, context-specific effects that must be balanced with their potential benefits.

Highlighted Articles

View Abstract

Navigate This Article