ArticleEukaryotic cell2015
Isoprenoid precursor biosynthesis is the essential metabolic role of the apicoplast during gametocytogenesis in Plasmodium falciparum.
Article in Eukaryotic cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 55 citations in OpenAlex.
- Review
- Targeting IspD for Anti-infective and Herbicide Development: Exploring Its Role, Mechanism, and Structural Insights.Journal of medicinal chemistry · 2025Review
- Apicoplast-Resident Processes: Exploiting the Chink in the Armour ofAdvances in pharmacological and pharmaceutical sciences · 2024Review
- Genetic validation ofeLife · 2023Article
- The interdependence of isoprenoid synthesis and apicoplast biogenesis in malaria parasites.PLoS pathogens · 2023Article
- New insights into apicoplast metabolism in blood-stage malaria parasites.Current opinion in microbiology · 2023Review
- Characterization of Domiphen Bromide as a New Fast-Acting Antiplasmodial Agent Inhibiting the Apicoplastidic Methyl Erythritol Phosphate Pathway.Pharmaceutics · 2022Article
- Enantiopure Benzofuran-2-carboxamides of 1-Aryltetrahydro-β-carbolines Are Potent AntimalarialsACS medicinal chemistry letters · 2022Article
- Apicoplast Dynamics DuringFrontiers in cellular and infection microbiology · 2022Review
- Apicoplast Journey and Its Essentiality as a Compartment for Malaria Parasite Survival.Frontiers in cellular and infection microbiology · 2022Article
- Lipoic Acid Metabolism as a Potential Chemotherapeutic Target AgainstFrontiers in chemistry · 2021Review
- Metabolomics profiling reveals new aspects of dolichol biosynthesis in Plasmodium falciparum.Scientific reports · 2020Article
- Biological Studies and Target Engagement of the 2- C-Methyl-d-Erythritol 4-Phosphate Cytidylyltransferase (IspD)-Targeting Antimalarial Agent (1 R,3 S)-MMV008138 and Analogs.ACS infectious diseases · 2018Article
- Adaptation of Plasmodium falciparum to its transmission environment.Nature ecology & evolution · 2018Article
- Plasmodium falciparum parasites overexpressing farnesyl diphosphate synthase/geranylgeranyl diphosphate synthase are more resistant to risedronate.Memorias do Instituto Oswaldo Cruz · 2018Article
- Validation of Putative Apicoplast-Targeting Drugs Using a Chemical Supplementation Assay in Cultured Human Malaria Parasites.Antimicrobial agents and chemotherapy · 2018Article
- MEPicides: potent antimalarial prodrugs targeting isoprenoid biosynthesis.Scientific reports · 2017Article
- Genomics of apicomplexan parasites.Critical reviews in biochemistry and molecular biology · 2017Review
- Herbicidal properties of antimalarial drugs.Scientific reports · 2017Article
- The apicoplast: now you see it, now you don't.International journal for parasitology · 2017Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The malaria parasite harbors a relict plastid called the apicoplast and its discovery opened a new avenue for drug discovery and development due to its unusual, nonmammalian metabolism. The apicoplast is essential during the asexual intraerythrocytic and hepatic stages of the parasite, and there is strong evidence supporting its essential metabolic role during the mosquito stages of the parasite. Supply of the isoprenoid building blocks isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) is the essential metabolic function of the apicoplast during the asexual intraerythrocytic stages. However, the metabolic role of the apicoplast during gametocyte development, the malaria stages transmitted to the mosquito, remains unknown. In this study, we showed that production of IPP for isoprenoid biosynthesis is the essential metabolic function of the apicoplast during gametocytogenesis, by obtaining normal gametocytes lacking the apicoplast when supplemented with IPP. When IPP supplementation was removed early in gametocytogenesis, developmental defects were observed, supporting the essential role of isoprenoids for normal gametocytogenesis. Furthermore, mosquitoes infected with gametocytes lacking the apicoplast developed fewer and smaller oocysts that failed to produce sporozoites. This finding further supports the essential role of the apicoplast in establishing a successful infection in the mosquito vector. Our study supports isoprenoid biosynthesis as a valid drug target for development of malaria transmission-blocking inhibitors.
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