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The role of cytochrome c in caspase activation in Drosophila melanogaster cells

The release of cytochrome c from mitochondria is necessary for the formation of the Apaf-1 apoptosome and subsequent activation of caspase-9 in mammalian cells. However, the role of cytochrome c in caspase activation in Drosophila cells is not well understood. We demonstrate here that cytochrome c r...

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Autores principales: Dorstyn, Loretta, Read, Stuart, Cakouros, Dimitrios, Huh, Jun R., Hay, Bruce A., Kumar, Sharad
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173478/
https://www.ncbi.nlm.nih.gov/pubmed/11901173
http://dx.doi.org/10.1083/jcb.200111107
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author Dorstyn, Loretta
Read, Stuart
Cakouros, Dimitrios
Huh, Jun R.
Hay, Bruce A.
Kumar, Sharad
author_facet Dorstyn, Loretta
Read, Stuart
Cakouros, Dimitrios
Huh, Jun R.
Hay, Bruce A.
Kumar, Sharad
author_sort Dorstyn, Loretta
collection PubMed
description The release of cytochrome c from mitochondria is necessary for the formation of the Apaf-1 apoptosome and subsequent activation of caspase-9 in mammalian cells. However, the role of cytochrome c in caspase activation in Drosophila cells is not well understood. We demonstrate here that cytochrome c remains associated with mitochondria during apoptosis of Drosophila cells and that the initiator caspase DRONC and effector caspase DRICE are activated after various death stimuli without any significant release of cytochrome c in the cytosol. Ectopic expression of the proapoptotic Bcl-2 protein, DEBCL, also fails to show any cytochrome c release from mitochondria. A significant proportion of cellular DRONC and DRICE appears to localize near mitochondria, suggesting that an apoptosome may form in the vicinity of mitochondria in the absence of cytochrome c release. In vitro, DRONC was recruited to a >700-kD complex, similar to the mammalian apoptosome in cell extracts supplemented with cytochrome c and dATP. These results suggest that caspase activation in insects follows a more primitive mechanism that may be the precursor to the caspase activation pathways in mammals.
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spelling pubmed-21734782008-05-01 The role of cytochrome c in caspase activation in Drosophila melanogaster cells Dorstyn, Loretta Read, Stuart Cakouros, Dimitrios Huh, Jun R. Hay, Bruce A. Kumar, Sharad J Cell Biol Article The release of cytochrome c from mitochondria is necessary for the formation of the Apaf-1 apoptosome and subsequent activation of caspase-9 in mammalian cells. However, the role of cytochrome c in caspase activation in Drosophila cells is not well understood. We demonstrate here that cytochrome c remains associated with mitochondria during apoptosis of Drosophila cells and that the initiator caspase DRONC and effector caspase DRICE are activated after various death stimuli without any significant release of cytochrome c in the cytosol. Ectopic expression of the proapoptotic Bcl-2 protein, DEBCL, also fails to show any cytochrome c release from mitochondria. A significant proportion of cellular DRONC and DRICE appears to localize near mitochondria, suggesting that an apoptosome may form in the vicinity of mitochondria in the absence of cytochrome c release. In vitro, DRONC was recruited to a >700-kD complex, similar to the mammalian apoptosome in cell extracts supplemented with cytochrome c and dATP. These results suggest that caspase activation in insects follows a more primitive mechanism that may be the precursor to the caspase activation pathways in mammals. The Rockefeller University Press 2002-03-18 /pmc/articles/PMC2173478/ /pubmed/11901173 http://dx.doi.org/10.1083/jcb.200111107 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Dorstyn, Loretta
Read, Stuart
Cakouros, Dimitrios
Huh, Jun R.
Hay, Bruce A.
Kumar, Sharad
The role of cytochrome c in caspase activation in Drosophila melanogaster cells
title The role of cytochrome c in caspase activation in Drosophila melanogaster cells
title_full The role of cytochrome c in caspase activation in Drosophila melanogaster cells
title_fullStr The role of cytochrome c in caspase activation in Drosophila melanogaster cells
title_full_unstemmed The role of cytochrome c in caspase activation in Drosophila melanogaster cells
title_short The role of cytochrome c in caspase activation in Drosophila melanogaster cells
title_sort role of cytochrome c in caspase activation in drosophila melanogaster cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173478/
https://www.ncbi.nlm.nih.gov/pubmed/11901173
http://dx.doi.org/10.1083/jcb.200111107
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