Aquaporin-4 mediated RONS transport under membrane lipid peroxidation: Atomic-scale mechanistic insights

Area of Science:

• Biophysics
• Membrane Biology
• Computational Biology

Background:

• Aquaporin-4 (AQP4) facilitates water transport and can transport reactive oxygen and nitrogen species (RONS).
• Oxidative stress and lipid peroxidation are implicated in cellular dysfunction, but their effect on AQP4-mediated RONS transport is unclear.

Purpose of the Study:

• To investigate the impact of varying degrees of lipid peroxidation on AQP4 structure and RONS transport.
• To elucidate the mechanisms by which peroxidized lipids affect AQP4-RONS interactions and transmembrane behavior.

Main Methods:

• Molecular dynamics simulations
• Free energy calculations
• Computational electrophysiology

Main Results:

• Lipid peroxidation significantly alters AQP4-lipid interactions and the membrane microenvironment.
• Changes in the lipid environment modulate the accessibility and passage of RONS through the AQP4 channel.
• Specific peroxidized lipid derivatives (POPC, POPE) influence AQP4's RONS transport propensity.

Conclusions:

• Lipid peroxidation plays a crucial role in modulating AQP4 channel function under oxidative stress.
• Altered lipid-protein interactions under oxidative conditions impact transmembrane RONS transport.
• Findings provide a mechanistic basis for understanding redox-related transport phenomena involving AQP4.