| Autor: |
Matthias Paulus Wagner, Pauline Formaglio, Olivier Gorgette, Jerzy Michal Dziekan, Christèle Huon, Isabell Berneburg, Stefan Rahlfs, Jean-Christophe Barale, Sheldon I. Feinstein, Aron B. Fisher, Didier Ménard, Zbynek Bozdech, Rogerio Amino, Lhousseine Touqui, Chetan E. Chitnis |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 39, Iss 11, Pp 110923- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2022.110923 |
| Popis: |
Summary: The uptake and digestion of host hemoglobin by malaria parasites during blood-stage growth leads to significant oxidative damage of membrane lipids. Repair of lipid peroxidation damage is crucial for parasite survival. Here, we demonstrate that Plasmodium falciparum imports a host antioxidant enzyme, peroxiredoxin 6 (PRDX6), during hemoglobin uptake from the red blood cell cytosol. PRDX6 is a lipid-peroxidation repair enzyme with phospholipase A2 (PLA2) activity. Inhibition of PRDX6 with a PLA2 inhibitor, Darapladib, increases lipid-peroxidation damage in the parasite and disrupts transport of hemoglobin-containing vesicles to the food vacuole, causing parasite death. Furthermore, inhibition of PRDX6 synergistically reduces the survival of artemisinin-resistant parasites following co-treatment of parasite cultures with artemisinin and Darapladib. Thus, PRDX6 is a host-derived drug target for development of antimalarial drugs that could help overcome artemisinin resistance. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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