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The role of Plasmodium V-ATPase in vacuolar physiology and antimalarial drug uptake.

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posted on 2023-07-24, 09:25 authored by Arne Alder, Cecilia P Sanchez, Matthew RG Russell, Lucy M Collinson, Michael Lanzer, Michael J Blackman, Tim-Wolf Gilberger, Joachim M Matz
To ensure their survival in the human bloodstream, malaria parasites degrade up to 80% of the host erythrocyte hemoglobin in an acidified digestive vacuole. Here, we combine conditional reverse genetics and quantitative imaging approaches to demonstrate that the human malaria pathogen Plasmodium falciparum employs a heteromultimeric V-ATPase complex to acidify the digestive vacuole matrix, which is essential for intravacuolar hemoglobin release, heme detoxification, and parasite survival. We reveal an additional function of the membrane-embedded V-ATPase subunits in regulating morphogenesis of the digestive vacuole independent of proton translocation. We further show that intravacuolar accumulation of antimalarial chemotherapeutics is surprisingly resilient to severe deacidification of the vacuole and that modulation of V-ATPase activity does not affect parasite sensitivity toward these drugs.

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Crick (Grant ID: CC2129, Grant title: Blackman CC2129) Crick (Grant ID: CC1076, Grant title: STP Electron Microscopy)

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