Phospholipid Asymmetry in Biological Membranes: Is the Role of Phosphatidylethanolamine Underappreciated?

The asymmetric distribution of phospholipids in cell membranes has been the focus of a lot of important research keeping its biological importance in mind. Most of this research is focused on phosphatidylserine (PS) since it is an apoptotic marker, and there is a robust and easy method available its selective quantification. The aim of this commentary is to argue in favour of another highly abundant membrane lipid, phosphatidylethanolamine (PE) almost always associated with PS. PE has one of the smallest headgroups and shows distinctly asymmetric transbilayer distribution. It is a neutral aminophospholipid and capable of a vastly wider range of interactions as seen in its unique ability to act as a molecular chaperone, implicated role in disease biology and its possible role as an anti-cancer target. There are ample evidences to the fact that PE may also bind to Annexin V (ANV), the PS-specific probe, at higher than 10 mol% PE concentrations and absence of Ca2+ ions. An update of the major takeaways from the literature regarding PE asymmetry is also provided.