Role of Oxidized Lipids in Permeation of H2O2 Through a Lipid Membrane: Molecular Mechanism of an Inhibitor to Promoter Switch.

H2O2 permeation through a cell membrane significantly affects living organisms, and permeation is controlled by the physico-chemical nature of lipids and other membrane components. We investigated the molecular relationship between H2O2 permeation and lipid membrane structure using three oxidized lipids. POVPC and PazePC act as intra- and inter-molecular permeation promoters, respectively; however, their underlying mechanisms were different. The former changed the partition equilibrium, while the latter changed the permeation pathway. PoxnoPC inhibited permeation under our experimental conditions via an intra-molecular configuration change. Thus, both intra- and inter-molecular processes were found to control the role of oxidized lipids as inhibitors and promoters towards H2O2 permeation with different mechanisms depending on structure and composition. Here, we identified two independent H2O2 permeation routes: (i) permeation through lipid membrane with increased partition coefficient by intra-molecular configurational change and (ii) diffusion through pores (water channels) formed by inter-molecular configurational change of oxidized lipids. We provide new insight into how biological cells control permeation of molecules through intra- and inter-molecular configurational changes in the lipid membrane. Thus, by employing a rational design for both oxidized lipids and other components, the permeation behaviour of H2O2 and other ions and molecules through a lipid membrane could be controlled.