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Inward cholesterol gradient of the membrane system installed by malaria parasites in normal and sickle erythrocytes



Fuyuki Tokumasu, Georgeta Crivat, Hans Ackerman, Jeeseong C. Hwang, Thomas Wellems


Plasmodium falciparum (Pf) infection remodels the human erythrocyte with new membrane systems, including a modified host erythrocyte membrane (EM), a parasitophorous vacuole membrane (PVM), a tubulovesicular network (TVN), and Maurer's clefts (MC). Here we report on the relative cholesterol contents of these membranes in parasitized normal (HbAA) and hemoglobin S-containing (HbAS, HbAS) erythrocytes. Results from fluorescence lifetime imaging microscopy (FLIM) experiments with a cholesterol-sensitive fluorophore show that membrane cholesterol levels in parasitized erythrocytes (pRBC) decrease inwardly from the EM, to the MC/TVN, to the PVM, and finally to the parasite membrane (PM). Cholesterol depletion of pRBC by methyl-Β-cyclodextrin treatment caused a collapse of this gradient. Lipid and cholesterol exchange data suggest that the cholesterol gradient involves a dilution effect from non-sterol lipids produced by the parasite. FLIM signals from the PVM or PM showed little or no difference between parasitized HbAA vs HbS-containing erythrocytes that differed in lipid content, suggesting that malaria parasites may regulate the cholesterol contents of the PVM and PM independently of levels in the host cell membrane. Cholesterol levels may affect raft structures and the membrane trafficking and sorting functions that support Pf survival in HbAA, HbAS and HbSS erythrocytes.
Journal of Cell Biology


Plasmodium falciparum, human erythrocytes, membrane modifications, fluorescence lifetime microscopy, cyclodextrin cholesterol depletion


Tokumasu, F. , Crivat, G. , Ackerman, H. , Hwang, J. and Wellems, T. (2014), Inward cholesterol gradient of the membrane system installed by malaria parasites in normal and sickle erythrocytes, Journal of Cell Biology, [online],, (Accessed May 23, 2024)


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Created May 28, 2014, Updated October 12, 2021