ArticlePloS one2019
Mitochondrial type II NADH dehydrogenase of Plasmodium falciparum (PfNDH2) is dispensable in the asexual blood stages.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Genomic heterogeneity of NAD(P)H dehydrogenase predisposes Cryptosporidium to clofazimine resistance.Nature microbiology · 2026Article
- Article
- Widespread genomic heterogeneity at the type II NAD(P)H dehydrogenase locus predisposesbioRxiv : the preprint server for biology · 2025Article
- Targeting Mitochondrial Function inInternational journal of molecular sciences · 2025Review
- Reactions ofInternational journal of molecular sciences · 2025Article
- The essential genome ofScience (New York, N.Y.) · 2025Article
- Targeting Malaria's Achilles' Heels: A Review of Plasmodium Life Cycle Vulnerabilities for Drug Discovery.Current topics in medicinal chemistry · 2025Review
- Systematic in vitro evolution inScience (New York, N.Y.) · 2024Article
- New antimalarial iromycin analogs produced by Streptomyces sp. RBL-0292.The Journal of antibiotics · 2024Article
- Mitochondrial CytochromeTropical medicine and infectious disease · 2024Review
- Plasmodium falciparum utilizes pyrophosphate to fuel an essential proton pump in the ring stage and the transition to trophozoite stage.PLoS pathogens · 2023Article
- Structure of complex III with bound antimalarial agent CK-2-68 provides insights into selective inhibition of Plasmodium cytochrome bcThe Journal of biological chemistry · 2023Article
- A screen of drug-like molecules identifies chemically diverse electron transport chain inhibitors in apicomplexan parasites.PLoS pathogens · 2023Article
- Aurachins, Bacterial Antibiotics Interfering with Electron Transport Processes.Antibiotics (Basel, Switzerland) · 2023Review
- Malaria therapeutics: are we close enough?Parasites & vectors · 2023Review
- Nornidulin, A New Inhibitor ofPharmaceuticals (Basel, Switzerland) · 2023Article
- Structure-activity relationships ofExpert opinion on drug discovery · 2022Article
- Metabolic changes accompanying the loss of fumarate hydratase and malate-quinone oxidoreductase in the asexual blood stage of Plasmodium falciparum.The Journal of biological chemistry · 2022Article
- Transcriptional changes in Plasmodium falciparum upon conditional knock down of mitochondrial ribosomal proteins RSM22 and L23.PloS one · 2022Article
- Design, synthesis, and biological evaluation of multiple targeting antimalarials.Acta pharmaceutica Sinica. B · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The battle against malaria has been substantially impeded by the recurrence of drug resistance in Plasmodium falciparum, the deadliest human malaria parasite. To counter the problem, novel antimalarial drugs are urgently needed, especially those that target unique pathways of the parasite, since they are less likely to have side effects. The mitochondrial type II NADH dehydrogenase (NDH2) of P. falciparum, PfNDH2 (PF3D7_0915000), has been considered a good prospective antimalarial drug target for over a decade, since malaria parasites lack the conventional multi-subunit NADH dehydrogenase, or Complex I, present in the mammalian mitochondrial electron transport chain (mtETC). Instead, Plasmodium parasites contain a single subunit NDH2, which lacks proton pumping activity and is absent in humans. A significant amount of effort has been expended to develop PfNDH2 specific inhibitors, yet the essentiality of PfNDH2 has not been convincingly verified. Herein, we knocked out PfNDH2 in P. falciparum via a CRISPR/Cas9 mediated approach. Deletion of PfNDH2 does not alter the parasite's susceptibility to multiple mtETC inhibitors, including atovaquone and ELQ-300. We also show that the antimalarial activity of the fungal NDH2 inhibitor HDQ and its new derivative CK-2-68 is due to inhibition of the parasite cytochrome bc1 complex rather than PfNDH2. These compounds directly inhibit the ubiquinol-cytochrome c reductase activity of the malarial bc1 complex. Our results suggest that PfNDH2 is not likely a good antimalarial drug target.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.