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Disruption of a mitochondrial protease machinery in Plasmodium falciparum is an intrinsic signal for parasite cell death

The ATP-dependent ClpQY protease system in Plasmodium falciparum is a prokaryotic machinery in the parasite. In the present study, we have identified the complete ClpQY system in P. falciparum and elucidated its functional importance in survival and growth of asexual stage parasites. We characterize...

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Autores principales: Rathore, S, Jain, S, Sinha, D, Gupta, M, Asad, M, Srivastava, A, Narayanan, M S, Ramasamy, G, Chauhan, V S, Gupta, D, Mohmmed, A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223699/
https://www.ncbi.nlm.nih.gov/pubmed/22113196
http://dx.doi.org/10.1038/cddis.2011.118
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author Rathore, S
Jain, S
Sinha, D
Gupta, M
Asad, M
Srivastava, A
Narayanan, M S
Ramasamy, G
Chauhan, V S
Gupta, D
Mohmmed, A
author_facet Rathore, S
Jain, S
Sinha, D
Gupta, M
Asad, M
Srivastava, A
Narayanan, M S
Ramasamy, G
Chauhan, V S
Gupta, D
Mohmmed, A
author_sort Rathore, S
collection PubMed
description The ATP-dependent ClpQY protease system in Plasmodium falciparum is a prokaryotic machinery in the parasite. In the present study, we have identified the complete ClpQY system in P. falciparum and elucidated its functional importance in survival and growth of asexual stage parasites. We characterized the interaction of P. falciparum ClpQ protease (PfClpQ) and PfClpY ATPase components, and showed that a short stretch of residues at the C terminus of PfClpY has an important role in this interaction; a synthetic peptide corresponding to this region antagonizes this interaction and interferes with the functioning of this machinery in the parasite. Disruption of ClpQY function by this peptide caused hindrance in the parasite growth and maturation of asexual stages of parasites. Detailed analyses of cellular effects in these parasites showed features of apoptosis-like cell death. The peptide-treated parasites showed mitochondrial dysfunction and loss of mitochondrial membrane potential. Dysfunctioning of mitochondria initiated a cascade of reactions in parasites, including activation of VAD–FMK-binding proteases and nucleases, which resulted in apoptosis-like cell death. These results show functional importance of mitochondrial proteases in the parasite and involvement of mitochondria in programmed cell death in the malaria parasites.
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spelling pubmed-32236992011-12-15 Disruption of a mitochondrial protease machinery in Plasmodium falciparum is an intrinsic signal for parasite cell death Rathore, S Jain, S Sinha, D Gupta, M Asad, M Srivastava, A Narayanan, M S Ramasamy, G Chauhan, V S Gupta, D Mohmmed, A Cell Death Dis Original Article The ATP-dependent ClpQY protease system in Plasmodium falciparum is a prokaryotic machinery in the parasite. In the present study, we have identified the complete ClpQY system in P. falciparum and elucidated its functional importance in survival and growth of asexual stage parasites. We characterized the interaction of P. falciparum ClpQ protease (PfClpQ) and PfClpY ATPase components, and showed that a short stretch of residues at the C terminus of PfClpY has an important role in this interaction; a synthetic peptide corresponding to this region antagonizes this interaction and interferes with the functioning of this machinery in the parasite. Disruption of ClpQY function by this peptide caused hindrance in the parasite growth and maturation of asexual stages of parasites. Detailed analyses of cellular effects in these parasites showed features of apoptosis-like cell death. The peptide-treated parasites showed mitochondrial dysfunction and loss of mitochondrial membrane potential. Dysfunctioning of mitochondria initiated a cascade of reactions in parasites, including activation of VAD–FMK-binding proteases and nucleases, which resulted in apoptosis-like cell death. These results show functional importance of mitochondrial proteases in the parasite and involvement of mitochondria in programmed cell death in the malaria parasites. Nature Publishing Group 2011-11 2011-11-24 /pmc/articles/PMC3223699/ /pubmed/22113196 http://dx.doi.org/10.1038/cddis.2011.118 Text en Copyright © 2011 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Rathore, S
Jain, S
Sinha, D
Gupta, M
Asad, M
Srivastava, A
Narayanan, M S
Ramasamy, G
Chauhan, V S
Gupta, D
Mohmmed, A
Disruption of a mitochondrial protease machinery in Plasmodium falciparum is an intrinsic signal for parasite cell death
title Disruption of a mitochondrial protease machinery in Plasmodium falciparum is an intrinsic signal for parasite cell death
title_full Disruption of a mitochondrial protease machinery in Plasmodium falciparum is an intrinsic signal for parasite cell death
title_fullStr Disruption of a mitochondrial protease machinery in Plasmodium falciparum is an intrinsic signal for parasite cell death
title_full_unstemmed Disruption of a mitochondrial protease machinery in Plasmodium falciparum is an intrinsic signal for parasite cell death
title_short Disruption of a mitochondrial protease machinery in Plasmodium falciparum is an intrinsic signal for parasite cell death
title_sort disruption of a mitochondrial protease machinery in plasmodium falciparum is an intrinsic signal for parasite cell death
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223699/
https://www.ncbi.nlm.nih.gov/pubmed/22113196
http://dx.doi.org/10.1038/cddis.2011.118
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