Effects of oxygen depletion on transmembrane protein activities

Abstract

Effects of oxygen depletion on cellular membranes are still poorly understood. Amphiphilic molecules are known to modulate the plasma membrane lipid bilayer’s physical properties; in turn, mechanical properties of the lipid bilayer affect signal transduction through numerous mechanosensitive transmembrane proteins including ion channels, receptor tyrosine kinases, NADPH oxidases and G-protein coupled receptors. Thus, the concentration of oxygen in/at the lipid bilayer may modulate its mechanical properties. Here we propose that: (i) under hypoxia, the plasma membrane lipid bilayer would become oxygen depleted, (ii) depletion of oxygen molecules might induce mechanical stress in the lipid bilayer, and (iii) hypoxia-induced mechanical stress in the lipid bilayer activates mechanosensitive transmembrane proteins and downstream signaling pathways. We provide evidence – on the basis of published experimental data – that there can be links between oxygen depletioninduced mechanical stress in the membrane and activation of some mechanisms participating in oxygen sensing, including reactive oxygen species (ROS) produced by mitochondrial complex III, ROS generated at the plasma membrane by NADPH oxidases, ion channels of the transient receptor potential family and increase in intracellular Ca2+ and stabilization of hypoxia-inducible factor 1α (HIF-1α).