ArticlePLoS pathogens2013
Malaria parasite-synthesized heme is essential in the mosquito and liver stages and complements host heme in the blood stages of infection.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 172 citations in OpenAlex.
- The Plasmodium heme detoxification protein functions in mitochondrial protein synthesis.Nature communications · 2026Article
- Russian Dolls of Heme Metabolism in Malaria-Infected Red Blood Cells: Nested Vulnerabilities and Therapeutic Opportunities.Pathogens (Basel, Switzerland) · 2026Review
- Heme as activator and target for artemisinin: Towards multiple pharmacological bioactivity.Biochemistry and biophysics reports · 2026Review
- Biogenesis of CytochromesACS infectious diseases · 2025Article
- Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle.Nature communications · 2025Article
- Liver stage P. falciparum antigens highly targeted by CD4+ T cells in malaria-exposed Ugandan children.PLoS pathogens · 2025Article
- Targeting Malaria's Achilles' Heels: A Review of Plasmodium Life Cycle Vulnerabilities for Drug Discovery.Current topics in medicinal chemistry · 2025Review
- 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
- Article
- Complex Endosymbiosis II: The Nonphotosynthetic Plastid of Apicomplexa Parasites (The Apicoplast) and Its Integrated Metabolism.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Distinct evolution of type I glutamine synthetase in Plasmodium and its species-specific requirement.Nature communications · 2023Article
- Current advances in nanodrug delivery systems for malaria prevention and treatment.Discover nano · 2023Review
- Roles of the apicoplast across the life cycles of rodent and human malaria parasites.The Journal of eukaryotic microbiology · 2022Review
- Activity-based protein profiling of human andiScience · 2022Article
- Babesia, Theileria, Plasmodium and Hemoglobin.Microorganisms · 2022Article
- Malaria parasite heme biosynthesis promotes and griseofulvin protects against cerebral malaria in mice.Nature communications · 2022Article
- Autophagy Underlies the Proteostasis Mechanisms of Artemisinin Resistance in P. falciparum Malaria.mBio · 2022Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heme metabolism is central to malaria parasite biology. The parasite acquires heme from host hemoglobin in the intraerythrocytic stages and stores it as hemozoin to prevent free heme toxicity. The parasite can also synthesize heme de novo, and all the enzymes in the pathway are characterized. To study the role of the dual heme sources in malaria parasite growth and development, we knocked out the first enzyme, δ-aminolevulinate synthase (ALAS), and the last enzyme, ferrochelatase (FC), in the heme-biosynthetic pathway of Plasmodium berghei (Pb). The wild-type and knockout (KO) parasites had similar intraerythrocytic growth patterns in mice. We carried out in vitro radiolabeling of heme in Pb-infected mouse reticulocytes and Plasmodium falciparum-infected human RBCs using [4-(14)C] aminolevulinic acid (ALA). We found that the parasites incorporated both host hemoglobin-heme and parasite-synthesized heme into hemozoin and mitochondrial cytochromes. The similar fates of the two heme sources suggest that they may serve as backup mechanisms to provide heme in the intraerythrocytic stages. Nevertheless, the de novo pathway is absolutely essential for parasite development in the mosquito and liver stages. PbKO parasites formed drastically reduced oocysts and did not form sporozoites in the salivary glands. Oocyst production in PbALASKO parasites recovered when mosquitoes received an ALA supplement. PbALASKO sporozoites could infect mice only when the mice received an ALA supplement. Our results indicate the potential for new therapeutic interventions targeting the heme-biosynthetic pathway in the parasite during the mosquito and liver stages.
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