ArticleThe Journal of biological chemistry2022
Metabolic changes accompanying the loss of fumarate hydratase and malate-quinone oxidoreductase in the asexual blood stage of Plasmodium falciparum.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 24 citations in OpenAlex.
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- Mechanisms of PfDNMT2 inhibition and PfATP6-mediated resistance to the antimalarial candidate SC83288 in Plasmodium falciparum.Nature communications · 2026Article
- Disruption of mitochondrial function in blood and sexual stages of Plasmodium falciparum by ferulenol.Parasites & vectors · 2025Article
- Recent advances in microbially derived chlorinated antiparasitic compounds.Molecular diversity · 2025Review
- Targeting Mitochondrial Function inInternational journal of molecular sciences · 2025Review
- Metabolomics Insights into Salivary Profile in Dogs withBiomolecules · 2025Article
- Generation of a new DiCre expressing parasite strain for functional characterization of Plasmodium falciparum genes in blood stages.Scientific reports · 2024Article
- tRNA lysidinylation is essential for the minimal translation system found in the apicoplast ofbioRxiv : the preprint server for biology · 2024Article
- Understanding the significance of oxygen tension on the biology of Plasmodium falciparum blood stages: From the human body to the laboratory.PLoS pathogens · 2024Review
- Transmission-Blocking Strategies for Malaria Eradication: Recent Advances in Small-Molecule Drug Development.Pharmaceuticals (Basel, Switzerland) · 2024Review
- A myzozoan-specific protein is an essential membrane-anchoring component of the succinate dehydrogenase complex inOpen biology · 2024Article
- Analysis ofBio-protocol · 2023Article
- Article
- New insights into apicoplast metabolism in blood-stage malaria parasites.Current opinion in microbiology · 2023Review
- Biochemical characterization and identification of ferulenol and embelin as potent inhibitors of malate:quinone oxidoreductase fromFrontiers in molecular biosciences · 2023Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
In the glucose-rich milieu of red blood cells, asexually replicating malarial parasites mainly rely on glycolysis for ATP production, with limited carbon flux through the mitochondrial tricarboxylic acid (TCA) cycle. By contrast, gametocytes and mosquito-stage parasites exhibit an increased dependence on the TCA cycle and oxidative phosphorylation for more economical energy generation. Prior genetic studies supported these stage-specific metabolic preferences by revealing that six of eight TCA cycle enzymes are completely dispensable during the asexual blood stages of Plasmodium falciparum, with only fumarate hydratase (FH) and malate-quinone oxidoreductase (MQO) being refractory to deletion. Several hypotheses have been put forth to explain the possible essentiality of FH and MQO, including their participation in a malate shuttle between the mitochondrial matrix and the cytosol. However, using newer genetic techniques like CRISPR and dimerizable Cre, we were able to generate deletion strains of FH and MQO in P. falciparum. We employed metabolomic analyses to characterize a double knockout mutant of FH and MQO (ΔFM) and identified changes in purine salvage and urea cycle metabolism that may help to limit fumarate accumulation. Correspondingly, we found that the ΔFM mutant was more sensitive to exogenous fumarate, which is known to cause toxicity by modifying and inactivating proteins and metabolites. Overall, our data indicate that P. falciparum is able to adequately compensate for the loss of FH and MQO, rendering them unsuitable targets for drug development.
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