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

• Verfasst von: Alder, Arne [VerfasserIn]
• Verfasst von: Sanchez, Cecilia P. [VerfasserIn]
• Verfasst von: Russell, Matthew R. G. [VerfasserIn]
• Verfasst von: Collinson, Lucy M. [VerfasserIn]
• Verfasst von: Lanzer, Michael [VerfasserIn]
• Verfasst von: Blackman, Michael J. [VerfasserIn]
• Verfasst von: Gilberger, Tim-Wolf [VerfasserIn]
• Verfasst von: Matz, Joachim M. [VerfasserIn]
• Titel: The role of Plasmodium V-ATPase in vacuolar physiology and antimalarial drug uptake
• Verf.angabe: Arne Alder, Cecilia P. Sanchez, Matthew R.G. Russell, Lucy M. Collinson, Michael Lanzer, Michael J. Blackman, Tim-Wolf Gilberger, and Joachim M. Matz
• E-Jahr: 2023
• Jahr: July 18, 2023
• Umfang: 12 S.
• Illustrationen: Illustrationen
• Fussnoten: Veröffentlicht: 18. Juli 2023 ; Gesehen am 10.01.2024
• Titel Quelle: Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America
• Ort Quelle: Washington, DC : National Acad. of Sciences, 1915
• Jahr Quelle: 2023
• Band/Heft Quelle: 120(2023), 30, Artikel-ID e2306420120, Seite 1-12
• ISSN Quelle: 1091-6490
• DOI: doi:10.1073/pnas.2306420120
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1877646369

Abstract

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.