ArticleCell death & disease2011
Drug-induced permeabilization of parasite's digestive vacuole is a key trigger of programmed cell death in Plasmodium falciparum.
Article in Cell death & disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
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- Chloroquine induces eryptosis inFrontiers in cellular and infection microbiology · 2025Article
- Cell Death ofPathogens (Basel, Switzerland) · 2024Article
- Magic bullets, magic shields, and antimicrobials in between.Pharmaceutical science advances · 2023Review
- Dual role of an essential HtrA2/Omi protease in the human malaria parasite: Maintenance of mitochondrial homeostasis and induction of apoptosis-like cell death under cellular stress.PLoS pathogens · 2022Article
- Calcium in the Backstage of Malaria Parasite Biology.Frontiers in cellular and infection microbiology · 2021Review
- Methods Used to Investigate theFrontiers in cellular and infection microbiology · 2021Review
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- 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
- Uptake of a fluorescently tagged chloroquine analogue is reduced in CQ-resistant compared to CQ-sensitive Plasmodium falciparum parasites.Malaria journal · 2019Article
- Article
- Evidence for Regulation of Hemoglobin Metabolism and Intracellular Ionic Flux by the Plasmodium falciparum Chloroquine Resistance Transporter.Scientific reports · 2018Article
- Chloroquine exposure triggers distinct cellular responses in sensitive versus resistant Plasmodium falciparum parasites.Scientific reports · 2018Article
- High-Content Screening of the Medicines for Malaria Venture Pathogen Box for Plasmodium falciparum Digestive Vacuole-Disrupting Molecules Reveals Valuable Starting Points for Drug Discovery.Antimicrobial agents and chemotherapy · 2018Article
- Anti-plasmodial and Chloroquine Resistance Suppressive Effects of Embelin.Pharmacognosy magazine · 2017Article
- Overcoming Chloroquine Resistance in Malaria: Design, Synthesis, and Structure-Activity Relationships of Novel Hybrid Compounds.Antimicrobial agents and chemotherapy · 2016Article
- Subverting lysosomal function inMicrobial cell (Graz, Austria) · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Having previously characterized chloroquine (CQ)-induced programmed cell death (PCD) hallmarks in the malaria parasite Plasmodium falciparum and delineating a pathway linking these features, the roles of non-classical mediators were investigated in this paper. It was shown that the later stages of this pathway are Ca(2+)-dependent and transcriptionally regulated. Moreover, it was demonstrated for the first time that micromolar concentrations of CQ partially permeabilized the parasite's digestive vacuole (DV) membrane and that this important upstream event appears to precede mitochondrial dysfunction. This permeabilization of the DV occurred without rupture of the DV membrane and was reminiscent of lysosome-mediated cell death in mammalian cells. As such micromolar concentrations of CQ are found in the patient's plasma after initial CQ loading, this alludes to a clinically relevant antimalarial mechanism of the drug which has yet to be recognized. Furthermore, other 'non-antimalarial' lysosomotropic compounds were also shown to cause DV permeabilization, triggering PCD in both CQ-sensitive and -resistant parasites. These findings present new avenues for antimalarial developments, which induce DV destabilization to kill parasites.
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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.