ArticleProceedings of the National Academy of Sciences of the United States of America2008
Four distinct pathways of hemoglobin uptake in the malaria parasite Plasmodium falciparum.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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89 citing papers in PubMed, 188 citations in OpenAlex.
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- Heme processing in the malaria parasite, Plasmodium falciparum: a time-dependent basal-level analysis.Communications biology · 2025Article
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- The Digestive Vacuole of the Malaria Parasite: A Specialized Lysosome.Pathogens (Basel, Switzerland) · 2024Review
- Detection of Developmental Asexual Stage-Specific RNA Editing Events inMicroorganisms · 2024Article
- Hemoglobin uptake and utilization by human protozoan parasites: a review.Frontiers in cellular and infection microbiology · 2023Review
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- Autophagy Underlies the Proteostasis Mechanisms of Artemisinin Resistance in P. falciparum Malaria.mBio · 2022Article
- The Plasmodium falciparum ABC transporter ABCI3 confers parasite strain-dependent pleiotropic antimalarial drug resistance.Cell chemical biology · 2022Article
29 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
During the bloodstage of malaria infection, the parasite internalizes and degrades massive amounts of hemoglobin from the host red blood cell. Using serial thin-section electron microscopy and three-dimensional reconstruction, we demonstrate four independent, but partially overlapping, hemoglobin-uptake processes distinguishable temporally, morphologically, and pharmacologically. Early ring-stage parasites undergo a profound morphological transformation in which they fold, like a cup, onto themselves and in so doing take a large first gulp of host cell cytoplasm. This event, which we term the "Big Gulp," appears to be independent of actin polymerization and marks the first step in biogenesis of the parasite's lysosomal compartment-the food vacuole. A second, previously identified uptake process, uses the cytostome, a well characterized and morphologically distinct structure at the surface of the parasite. This process is more akin to classical endocytosis, giving rise to small (<0.004 fl) vesicles that are marked by the early endosomal regulatory protein Rab5a. A third process, also arising from cytostomes, creates long thin tubes previously termed cytostomal tubes in an actin-dependent manner. The fourth pathway, which we term phagotrophy, is similar to the Big Gulp in that it more closely resembles phagocytosis, except that phagotrophy does not require actin polymerization. Each of these four processes has aspects that are unique to Plasmodium, thus opening avenues to antimalarial therapy.
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