Fig 7. Proposed model of maintenance of phospholipid asymmetry in a Plasmodium falciparum-infected erythrocyte, based on the findings of this study.

(1) The parasite sequesters cholesterol from the host RBC, leaving the RBC membrane depleted of cholesterol (2) Parasite infection also causes an increase in Ca²⁺ influx to the RBC from the external environment, and potentially by leakage from the PV (3) Ca²⁺ ions activate the scramblase enzymes, while repression by cholesterol is removed (4) Scramblase activation results in exposure of PS in the outer membrane leaflet (5) Exposed PS acts as a recognition signal for monocytes. Most iRBCs are rescued from phagocytosis by compensatory mechanisms (in yellow) including efflux and/or parasite uptake of Ca²⁺ ions by host or parasite channels, and flippase-mediated internalisation of PS. PS = phosphatidylserine; PE = phosphatidylethanolamine; PC = phosphatidylcholine; PPM = parasite plasma membrane; PV = parasitophorous vacuole; PVM = parasitophorous vacuole membrane; ATP = adenosine triphosphate; ADP = adenosine diphosphate.