ArticleThe Journal of biological chemistry2012
Direct tests of enzymatic heme degradation by the malaria parasite Plasmodium falciparum.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 68 citations in OpenAlex.
- Parasite maturation and host serum iron influence the labile iron pool of erythrocyte stage Plasmodium falciparum.British journal of haematology · 2013Trial
- Aptamer-Based Biosensors for the Detection of Malaria.Biosensors · 2026Review
- Hemoglobin Digestion Genes Are Conserved in Lizard-InfectiveEcology and evolution · 2026Article
- Aspartyl protease inhibition interferes with Plasmodium falciparum asexual blood-stage and early gametocyte development.Malaria journal · 2025Article
- Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis.eLife · 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
- Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis.bioRxiv : the preprint server for biology · 2024Article
- Heme metabolism in Strigomonas culicis: Implications of HThe Journal of biological chemistry · 2024Article
- Identification of a divalent metal transporter required for cellular iron metabolism in malaria parasites.bioRxiv : the preprint server for biology · 2024Article
- Let it glow: genetically encoded fluorescent reporters in Plasmodium.Malaria journal · 2024Review
- Plasmodium yoelii iron transporter PyDMT1 interacts with host ferritin and is required in full activity for malarial pathogenesis.BMC biology · 2023Article
- Discriminant Analysis PCA-LDA Assisted Surface-Enhanced Raman Spectroscopy for Direct Identification of Malaria-Infected Red Blood Cells.Methods and protocols · 2022Article
- The Antagonizing Role of Heme in the Antimalarial Function of Artemisinin: Elevating Intracellular Free Heme Negatively Impacts Artemisinin Activity inMolecules (Basel, Switzerland) · 2022Article
- Review of Microdevices for Hemozoin-Based Malaria Detection.Biosensors · 2022Review
- Orchestrating a heist: uptake and storage of metals by apicomplexan parasites.Microbiology (Reading, England) · 2021Article
- Heme Detoxification in the Malaria Parasite: A Target for Antimalarial Drug Development.Accounts of chemical research · 2021Review
- Article
- Renal control of disease tolerance to malaria.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Inorganic Complexes and Metal-Based Nanomaterials for Infectious Disease Diagnostics.Chemical reviews · 2019Review
- The Asp99-Arg188 salt bridge of the Pseudomonas aeruginosa HemO is critical in allowing conformational flexibility during catalysis.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Malaria parasites generate vast quantities of heme during blood stage infection via hemoglobin digestion and limited de novo biosynthesis, but it remains unclear if parasites metabolize heme for utilization or disposal. Recent in vitro experiments with a heme oxygenase (HO)-like protein from Plasmodium falciparum suggested that parasites may enzymatically degrade some heme to the canonical HO product, biliverdin (BV), or its downstream metabolite, bilirubin (BR). To directly test for BV and BR production by P. falciparum parasites, we DMSO-extracted equal numbers of infected and uninfected erythrocytes and developed a sensitive LC-MS/MS assay to quantify these tetrapyrroles. We found comparable low levels of BV and BR in both samples, suggesting the absence of HO activity in parasites. We further tested live parasites by targeted expression of a fluorescent BV-binding protein within the parasite cytosol, mitochondrion, and plant-like plastid. This probe could detect exogenously added BV but gave no signal indicative of endogenous BV production within parasites. Finally, we recombinantly expressed and tested the proposed heme degrading activity of the HO-like protein, PfHO. Although PfHO bound heme and protoporphyrin IX with modest affinity, it did not catalyze heme degradation in vivo within bacteria or in vitro in UV absorbance and HPLC assays. These observations are consistent with PfHO's lack of a heme-coordinating His residue and suggest an alternative function within parasites. We conclude that P. falciparum parasites lack a canonical HO pathway for heme degradation and thus rely fully on alternative mechanisms for heme detoxification and iron acquisition during blood stage infection.
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