ArticleThe Journal of biological chemistry2014
The heme biosynthesis pathway is essential for Plasmodium falciparum development in mosquito stage but not in blood stages.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 178 citations in OpenAlex.
- The Plasmodium heme detoxification protein functions in mitochondrial protein synthesis.Nature communications · 2026Article
- Heme as activator and target for artemisinin: Towards multiple pharmacological bioactivity.Biochemistry and biophysics reports · 2026Review
- Biogenesis of CytochromesACS infectious diseases · 2025Article
- Hemozoin: a waste product after heme detoxification?Parasites & vectors · 2025Article
- Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle.Nature communications · 2025Article
- The dynamin-related protein PfDyn2 is essential for both apicoplast and mitochondrial fission inmBio · 2025Article
- Targeting Malaria's Achilles' Heels: A Review of Plasmodium Life Cycle Vulnerabilities for Drug Discovery.Current topics in medicinal chemistry · 2025Review
- Artemisinin-resistant Plasmodium falciparum Kelch13 mutant proteins display reduced heme-binding affinity and decreased artemisinin activation.Communications biology · 2024Article
- Identification of a divalent metal transporter required for cellular iron metabolism in malaria parasites.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Biogenesis of cytochromesbioRxiv : the preprint server for biology · 2024Article
- Host cell CRISPR genomics and modelling reveal shared metabolic vulnerabilities in the intracellular development of Plasmodium falciparum and related hemoparasites.Nature communications · 2024Article
- Identification of a divalent metal transporter required for cellular iron metabolism in malaria parasites.bioRxiv : the preprint server for biology · 2024Article
- Apicoplast-Resident Processes: Exploiting the Chink in the Armour ofAdvances in pharmacological and pharmaceutical sciences · 2024Review
- Extracellular vesicles could be a putative posttranscriptional regulatory mechanism that shapes intracellular RNA levels in Plasmodium falciparum.Nature communications · 2023Article
- TheeLife · 2023Article
- Direct tests of cytochromeProceedings of the National Academy of Sciences of the United States of America · 2023Article
- New insights into apicoplast metabolism in blood-stage malaria parasites.Current opinion in microbiology · 2023Review
- Direct Tests of Cytochrome Function in the Electron Transport Chain of Malaria Parasites.bioRxiv : the preprint server for biology · 2023Article
- Review
- Babesia, Theileria, Plasmodium and Hemoglobin.Microorganisms · 2022Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Heme is an essential cofactor for aerobic organisms. Its redox chemistry is central to a variety of biological functions mediated by hemoproteins. In blood stages, malaria parasites consume most of the hemoglobin inside the infected erythrocytes, forming nontoxic hemozoin crystals from large quantities of heme released during digestion. At the same time, the parasites possess a heme de novo biosynthetic pathway. This pathway in the human malaria parasite Plasmodium falciparum has been considered essential and is proposed as a potential drug target. However, we successfully disrupted the first and last genes of the pathway, individually and in combination. These knock-out parasite lines, lacking 5-aminolevulinic acid synthase and/or ferrochelatase (FC), grew normally in blood-stage culture and exhibited no changes in sensitivity to heme-related antimalarial drugs. We developed a sensitive LC-MS/MS assay to monitor stable isotope incorporation into heme from its precursor 5-[(13)C4]aminolevulinic acid, and this assay confirmed that de novo heme synthesis was ablated in FC knock-out parasites. Disrupting the FC gene also caused no defects in gametocyte generation or maturation but resulted in a greater than 70% reduction in male gamete formation and completely prevented oocyst formation in female Anopheles stephensi mosquitoes. Our data demonstrate that the heme biosynthesis pathway is not essential for asexual blood-stage growth of P. falciparum parasites but is required for mosquito transmission. Drug inhibition of pathway activity is therefore unlikely to provide successful antimalarial therapy. These data also suggest the existence of a parasite mechanism for scavenging host heme to meet metabolic needs.
Indexed as
Identifiers
What OpenQuestion holds
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.