Phospholipid flip-flop in biogenic membranes: what is needed to connect opposite sides

Phospholipids are synthesized in biogenic membranes, but only on one leaflet of the bilayer. To support balanced growth of the membrane, phospholipid translocation, or flip-flop, has to occur. Though consensus has been reached that flip-flop is most likely mediated by (a) membrane-associated protein(s), a dedicated flippase has not been identified yet in any biogenic membrane. The characteristics of the flip-flop process are summarized, and possible mechanisms, including the need for a dedicated flippase, are discussed.