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

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 fal...

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Bibliographic Details
Main Authors: Alder, Arne (Author) , Sanchez, Cecilia P. (Author) , Russell, Matthew R. G. (Author) , Collinson, Lucy M. (Author) , Lanzer, Michael (Author) , Blackman, Michael J. (Author) , Gilberger, Tim-Wolf (Author) , Matz, Joachim M. (Author)
Format: Article (Journal)
Language:English
Published: July 18, 2023
In: Proceedings of the National Academy of Sciences of the United States of America
Year: 2023, Volume: 120, Issue: 30, Pages: 1-12
ISSN:1091-6490
DOI:10.1073/pnas.2306420120
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1073/pnas.2306420120
Verlag, kostenfrei, Volltext: https://www.pnas.org/doi/10.1073/pnas.2306420120
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Author Notes:Arne Alder, Cecilia P. Sanchez, Matthew R.G. Russell, Lucy M. Collinson, Michael Lanzer, Michael J. Blackman, Tim-Wolf Gilberger, and Joachim M. Matz
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Summary: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.
Item Description:Veröffentlicht: 18. Juli 2023
Gesehen am 10.01.2024
Physical Description:Online Resource
ISSN:1091-6490
DOI:10.1073/pnas.2306420120

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