Could CO2 be a player in a redox relay team?

Abstract

It has been established that hydrogen peroxide (H₂O₂) acts as a signalling messenger by triggering the reversible oxidation of redox-regulated proteins via a redox-relay provided by peroxiredoxins (Prdxs). Exceptionally high reactivity of Prdxs with H₂O₂ exceeding other thiols by orders of magnitude places Prdxs as sensors of H₂O₂ and distributers of oxidizing equivalents to specific thiol targets which can't be oxidized by H₂O₂ directly. By this mechanism the oxidative stress response can be achieved.

Despite its involvement in oxidative stress responses, H₂O₂ is continuously generated as a normal metabolite necessary for regular cell functioning. The challenge lies in understanding how the Prdx-dependent redox relay can differentiate between basal levels of H₂O₂ and excessive amounts that lead to oxidative stress.

Peroxymonocarbonate, an oxidant formed when H₂O₂ reacts with CO₂/HCO₃⁻, emerges as a potent cellular oxidant. The peroxymonocarbonate formation could be catalysed and then consumed at localised sites by certain thiol proteins. This mechanism could prevent H₂O₂ from reacting with Prdx, thereby averting the redox-relayed activation of regulatory thiol proteins and subsequent oxidative stress response below a certain level of H₂O₂.