Hydrogen peroxide transport by aquaporins: insights from molecular modeling and simulations

Abstract

Hydrogen peroxide (H2O2) is a key reactive oxygen species involved in cellular redox signaling and oxidative stress. Due to its polar nature, its transport across membranes is regulated by aquaporins (AQPs), membrane channels traditionally known for H2O transport. Certain AQPs, known as peroxiporins, facilitate selective H2O2 permeation, playing critical roles in mantaining redox homeostasis. This review summarizes insights from molecular dynamics (MD) simulations into the mechanisms of H2O2 transport through AQPs. Key structural regions, such as the selectivity filter (SF) and NPA motif, influence H2O2 permeation, with energy profiles revealing differences from H2O transport. While molecular mimicry suggests similarities in the movement of H2O and H2O2, specific interactions and energetic barriers highlight the complexity of the process. We highlight the need for integrating computational and experimental findings for further studies to unify mechanistic understanding and develop applications in redox biology.