ArticleProceedings of the National Academy of Sciences of the United States of America2012
Oriented nucleation of hemozoin at the digestive vacuole membrane in Plasmodium falciparum.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Serum lipids and lipoproteins in malaria--a systematic review and meta-analysis.Malaria journal · 2013Pooled it
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- Artificial intelligence-powered microscopy: Transforming the landscape of parasitology.Journal of microscopy · 2026Review
- Chemical propulsion of hemozoin crystal motion in malaria parasites.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Tafenoquine Disrupts Intraerythrocytic Stages of Malaria Parasites by Inhibiting Nonclassical Pathways of β-Hematin Nucleation and Growth.Biochemistry · 2025Article
- Towards a quantitative theory for transmission X-ray microscopy.Beilstein journal of nanotechnology · 2025Article
- Cryo-tomography and 3D Electron Diffraction Reveal the Polar Habit and Chiral Structure of the Malaria Pigment Crystal Hemozoin.ACS central science · 2024Article
- Magneto-optical assessment of Plasmodium parasite growth via hemozoin crystal size.Scientific reports · 2024Article
- The Digestive Vacuole of the Malaria Parasite: A Specialized Lysosome.Pathogens (Basel, Switzerland) · 2024Review
- Biodereplication of Antiplasmodial Extracts: Application of the Amazonian Medicinal PlantMolecules (Basel, Switzerland) · 2022Article
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- Antiplasmodial Cyclodecapeptides from Tyrothricin Share a Target with Chloroquine.Antibiotics (Basel, Switzerland) · 2022Article
- The Role of the Iron Protoporphyrins Heme and Hematin in the Antimalarial Activity of Endoperoxide Drugs.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Heme Detoxification in the Malaria Parasite: A Target for Antimalarial Drug Development.Accounts of chemical research · 2021Review
- Malaria Pigment Crystals: The Achilles' Heel of the Malaria Parasite.ChemMedChem · 2021Review
- Probing the Intracellular Bio-Nano Interface in Different Cell Lines with Gold Nanostars.Nanomaterials (Basel, Switzerland) · 2021Article
- Methods Used to Investigate theFrontiers in cellular and infection microbiology · 2021Review
- Mode of action of quinoline antimalarial drugs in red blood cells infected byProceedings of the National Academy of Sciences of the United States of America · 2019Article
- X-ray tomography shows the varying three-dimensional morphology of gold nanoaggregates in the cellular ultrastructure.Nanoscale advances · 2019Article
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heme detoxification is a critical step in the life cycle of malaria-causing parasites, achieved by crystallization into physiologically insoluble hemozoin. The mode of nucleation has profound implications for understanding the mechanism of action of antimalarial drugs that inhibit hemozoin growth. Several lines of evidence point to involvement of acylglycerol lipids in the nucleation process. Hemozoin crystals have been reported to form within lipid nanospheres; alternatively, it has been found in vitro that they are nucleated at an acylglycerol lipid-water interface. We have applied cryogenic soft X-ray tomography and three-dimensional electron microscopy to address the location and orientation of hemozoin crystals within the digestive vacuole (DV), as a signature of their nucleation and growth processes. Cryogenic soft X-ray tomography in the "water window" is particularly advantageous because contrast generation is based inherently on atomic absorption. We find that hemozoin nucleation occurs at the DV inner membrane, with crystallization occurring in the aqueous rather than lipid phase. The crystal morphology indicates a common {100} orientation facing the membrane as expected of templated nucleation. This is consistent with conclusions reached by X-ray fluorescence and diffraction in a companion work. Uniform dark spheres observed in the parasite were identified as hemoglobin transport vesicles. Their analysis supports a model of hemozoin nucleation primarily in the DV. Modeling of the contrast at the DV membrane indicates a 4-nm thickness with patches about three times thicker, possibly implicated in the nucleation.
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