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

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.