Regulated Transport of H2O2 across the Plasma Membrane by Aquaporin-8

When oxygen appeared on earth, living organisms had to swiftly take countermeasures to prevent lethal oxidative damage. The survivors did not miss the chance to exploit the ensuing redox gradient between the extracellular space and the cytosol for generating novel signaling paths or tuning existing ones. To allow these fundamental mechanisms, membranes impervious to non-gaseous reactive oxygen species now surround cells and most organelles. Therefore, to allow input of redox signals, these membranes must be equipped with regulated channels. This chapter describes one such protein, AQP8, a water channel that can transfer across the plasma membrane also H₂O₂ molecules generated in the extracellular space to regulate tyrosine kinase receptor signaling and redox homeostasis. An elegant two-step gating mechanism regulates H₂O₂ fluxes through AQP8, thus allowing signal boosting while limiting the risks of overoxidation.