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Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction Between Caspase 8 and Mitochondria

Human Immunodeficiency Virus (HIV) protease initiates apoptosis of HIV-infected cells by proteolytic cleavage of procaspase 8, creating a novel peptide termed casp8p41. Expression of casp8p41 alone is sufficient to initiate caspase-dependent cell death associated with mitochondrial depolarization. S...

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Autores principales: Algeciras-Schimnich, Alicia, Belzacq-Casagrande, Anne-Sophie, Bren, Gary D, Nie, Zilin, Taylor, Julie A, Rizza, Stacey A, Brenner, Catherine, Badley, Andrew D
Formato: Texto
Lenguaje:English
Publicado: Bentham Science Publishers Ltd. 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2548302/
https://www.ncbi.nlm.nih.gov/pubmed/18818773
http://dx.doi.org/10.2174/1874357900701010039
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author Algeciras-Schimnich, Alicia
Belzacq-Casagrande, Anne-Sophie
Bren, Gary D
Nie, Zilin
Taylor, Julie A
Rizza, Stacey A
Brenner, Catherine
Badley, Andrew D
author_facet Algeciras-Schimnich, Alicia
Belzacq-Casagrande, Anne-Sophie
Bren, Gary D
Nie, Zilin
Taylor, Julie A
Rizza, Stacey A
Brenner, Catherine
Badley, Andrew D
author_sort Algeciras-Schimnich, Alicia
collection PubMed
description Human Immunodeficiency Virus (HIV) protease initiates apoptosis of HIV-infected cells by proteolytic cleavage of procaspase 8, creating a novel peptide termed casp8p41. Expression of casp8p41 alone is sufficient to initiate caspase-dependent cell death associated with mitochondrial depolarization. Since casp8p41 does not contain the catalytic cysteine at position 360, the mechanism by which casp8p41 initiates apoptosis is unclear. We demonstrate that casp8p41 directly causes mitochondrial depolarization and release of cytochrome c with downstream caspase 9 activation. Moreover, death induced by casp8p41 requires the presence of mitochondria, and in intact cells, casp8p41 colocalizes with mitochondria. These results illuminate a novel mechanism of cell death induced by a caspase 8 cleavage fragment whereby mitochondrial interaction leads to depolarization and cytochrome c release.
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spelling pubmed-25483022008-09-23 Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction Between Caspase 8 and Mitochondria Algeciras-Schimnich, Alicia Belzacq-Casagrande, Anne-Sophie Bren, Gary D Nie, Zilin Taylor, Julie A Rizza, Stacey A Brenner, Catherine Badley, Andrew D Open Virol J Article Human Immunodeficiency Virus (HIV) protease initiates apoptosis of HIV-infected cells by proteolytic cleavage of procaspase 8, creating a novel peptide termed casp8p41. Expression of casp8p41 alone is sufficient to initiate caspase-dependent cell death associated with mitochondrial depolarization. Since casp8p41 does not contain the catalytic cysteine at position 360, the mechanism by which casp8p41 initiates apoptosis is unclear. We demonstrate that casp8p41 directly causes mitochondrial depolarization and release of cytochrome c with downstream caspase 9 activation. Moreover, death induced by casp8p41 requires the presence of mitochondria, and in intact cells, casp8p41 colocalizes with mitochondria. These results illuminate a novel mechanism of cell death induced by a caspase 8 cleavage fragment whereby mitochondrial interaction leads to depolarization and cytochrome c release. Bentham Science Publishers Ltd. 2007-12-27 /pmc/articles/PMC2548302/ /pubmed/18818773 http://dx.doi.org/10.2174/1874357900701010039 Text en 2007 Bentham Science Publishers Ltd. http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Algeciras-Schimnich, Alicia
Belzacq-Casagrande, Anne-Sophie
Bren, Gary D
Nie, Zilin
Taylor, Julie A
Rizza, Stacey A
Brenner, Catherine
Badley, Andrew D
Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction Between Caspase 8 and Mitochondria
title Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction Between Caspase 8 and Mitochondria
title_full Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction Between Caspase 8 and Mitochondria
title_fullStr Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction Between Caspase 8 and Mitochondria
title_full_unstemmed Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction Between Caspase 8 and Mitochondria
title_short Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction Between Caspase 8 and Mitochondria
title_sort analysis of hiv protease killing through caspase 8 reveals a novel interaction between caspase 8 and mitochondria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2548302/
https://www.ncbi.nlm.nih.gov/pubmed/18818773
http://dx.doi.org/10.2174/1874357900701010039
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