ArticlePloS one2011
Plasmodium falciparum metacaspase PfMCA-1 triggers a z-VAD-fmk inhibitable protease to promote cell death.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- An inclusive assessment of apoptosis mechanisms inCurrent research in parasitology & vector-borne diseases · 2025Review
- Cell Death ofPathogens (Basel, Switzerland) · 2024Article
- Profile of metacaspase gene expression in Plasmodium vivax field isolates from the Brazilian Amazon.Molecular biology reports · 2024Article
- Dissecting The role ofEmerging microbes & infections · 2022Article
- Plasmodium vivax metacaspase 1 (PvMCA1) catalytic domain is conserved in field isolates from Brazilian Amazon.Memorias do Instituto Oswaldo Cruz · 2021Article
- Article
- Symbiotic Origin of Apoptosis.Results and problems in cell differentiation · 2020Article
- Extracellular vesicles carrying lactate dehydrogenase induce suicide in increased population density of Plasmodium falciparum in vitro.Scientific reports · 2019Article
- Cell death in Leishmania.Parasite (Paris, France) · 2019Review
- Proteases as antimalarial targets: strategies for genetic, chemical, and therapeutic validation.The FEBS journal · 2017Review
- Genetic diversity of Plasmodium vivax metacaspase 1 and Plasmodium vivax multi-drug resistance 1 genes of field isolates from Mauritania, Sudan and Oman.Malaria journal · 2017Article
- WantedMicrobial cell (Graz, Austria) · 2015Review
- Disruption of cellular homeostasis induces organelle stress and triggers apoptosis like cell-death pathways in malaria parasite.Cell death & disease · 2015Article
- Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca²⁺-ATPase PfATP6.Memorias do Instituto Oswaldo Cruz · 2015Article
- Comparative structural analysis of the caspase family with other clan CD cysteine peptidases.The Biochemical journal · 2015Review
- Caspase-like proteins: Acanthamoeba castellanii metacaspase and Dictyostelium discoideum paracaspase, what are their functions?Journal of biosciences · 2014Review
- The Arabidopsis metacaspase9 degradome.The Plant cell · 2013Article
- The first suicides: a legacy inherited by parasitic protozoans from prokaryote ancestors.Parasites & vectors · 2013Review
- Article
- A process similar to autophagy is associated with cytocidal chloroquine resistance in Plasmodium falciparum.PloS one · 2013Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of proteolytic cell death pathways may circumvent drug resistance in deadly protozoan parasites such as Plasmodium falciparum and Leishmania. To this end, it is important to define the cell death pathway(s) in parasites and thus characterize proteases such as metacaspases (MCA), which have been reported to induce cell death in plants and Leishmania parasites. We, therefore, investigated whether the cell death function of MCA is conserved in different protozoan parasite species such as Plasmodium falciparum and Leishmania major, focusing on the substrate specificity and functional role in cell survival as compared to Saccharomyces cerevisae. Our results show that, similarly to Leishmania, Plasmodium MCA exhibits a calcium-dependent, arginine-specific protease activity and its expression in yeast induced growth inhibition as well as an 82% increase in cell death under oxidative stress, a situation encountered by parasites during the host or when exposed to drugs such as artemisins. Furthermore, we show that MCA cell death pathways in both Plasmodium and Leishmania, involve a z-VAD-fmk inhibitable protease. Our data provide evidence that MCA from both Leishmania and Plasmodium falciparum is able to induce cell death in stress conditions, where it specifically activates a downstream enzyme as part of a cell death pathway. This enzymatic activity is also induced by the antimalarial drug chloroquine in erythrocytic stages of Plasmodium falciparum. Interestingly, we found that blocking parasite cell death influences their drug sensitivity, a result which could be used to create therapeutic strategies that by-pass drug resistance mechanisms by acting directly on the innate pathways of protozoan cell death.
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