During regeneration, multiple signalling pathways act to coordinate the various processes required to regenerate an injured organ or body part. Both reactive oxygen species (ROS) and electric currents have been shown to modulate regeneration, but how they exert their effects, and whether their activities might intersect, is poorly understood. Here (p. 4582), Fernando Ferreira, Min Zhao and colleagues set out to address the potential interplay between ROS and bioelectric phenomena using the Xenopus tadpole tail regeneration model. They uncover a dual role for NADPH oxidases in regulating bioelectric activities: NADPH oxidase-driven electron flow induces membrane depolarisation, while the hydrogen peroxide produced leads to activation of sodium channels in cell membranes of the regeneration bud, with consequent effects on transepithelial potential and electric currents that mediate regeneration. Moreover, external application of hydrogen peroxide can induce tail regeneration during the refractory period in the tadpole’s life – when regeneration is normally blocked – as well as the formation of ectopic tails at injury sites during the regenerative period. Although the mechanisms by which bioelectric activities might modulate the cellular processes required for regeneration still require further investigation, this work links two previously unconnected regulators of regeneration and provides convincing evidence for redox-bioelectric integration in this context.
