Jens Peter Andersen
Phospholipid flippases constitute the largest subfamily of P-type ATPases and have in eukaryotic organisms evolved as a central transport system for selective translocation of phospholipids across biological membranes to generate membrane lipid asymmetry, a property essential for numerous cellular processes. The importance of flippases is highlighted by severe neurological disorders and liver diseases caused by flippase dysfunction in humans. The electrogenicity of phospholipid transport by flippases has not previously been explored. We demonstrated that phosphatidylserine translocation by the flippase ATP8A2 generates electrical current, resulting from specific steps in the flippase reaction cycle moving the charged lipid head group between the membrane bilayer leaflets, and that no charged substrate is being countertransported. These findings unravel key features of phospholipid flippases.