Bcl-2: A prime regulator of mitochondrial redox metabolism in cancer cells

Significance: Mitochondria play a critical role as death amplifiers during drug-induced apoptosis in cancer cells by providing pro-apoptotic factors that are released from the mitochondrial inter-membranous space upon the induction of mitochondrial outer membrane permeabilization. This intrinsic dea...

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Main Authors: Low, I., Kang, J., Pervaiz, Shazib
Format: Journal Article
Published: Mary Ann Liebert, Inc. Publishers 2011
Online Access:http://hdl.handle.net/20.500.11937/51225
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author Low, I.
Kang, J.
Pervaiz, Shazib
author_facet Low, I.
Kang, J.
Pervaiz, Shazib
author_sort Low, I.
building Curtin Institutional Repository
collection Online Access
description Significance: Mitochondria play a critical role as death amplifiers during drug-induced apoptosis in cancer cells by providing pro-apoptotic factors that are released from the mitochondrial inter-membranous space upon the induction of mitochondrial outer membrane permeabilization. This intrinsic death signaling pathway is the preferred mechanism employed by most anticancer compounds, and as such, resistance to drug-induced apoptosis is invariably associated with inhibition of mitochondrial death signaling network. The latter is a function of a balance between the pro- and the anti-apoptotic members of the Bcl-2 family. Bcl-2 is the prototype anti-apoptotic protein that localizes to the mitochondria and blocks the recruitment and activation of pro-apoptotic proteins, such as Bax, to the mitochondria. Recent Advances and Critical Issues: Recent evidence has highlighted a novel mechanism of anti-apoptotic activity of Bcl-2 in addition to its canonical activity in regulating mitochondrial outer membrane permeabilization. This novel activity is a function of cellular redox regulation, in particular, mitochondrial metabolism in cancer cells. Future Directions: Here we review the current state of our understanding of the death inhibitory activity of Bcl-2 and provide insight into the novel functional biology of this remarkable protein, which could have implications for designing innovative strategies to overcome the problem of drug resistance in the clinical settings. © Copyright 2011, Mary Ann Liebert, Inc. 2011.
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spelling curtin-20.500.11937-512252017-09-13T15:34:51Z Bcl-2: A prime regulator of mitochondrial redox metabolism in cancer cells Low, I. Kang, J. Pervaiz, Shazib Significance: Mitochondria play a critical role as death amplifiers during drug-induced apoptosis in cancer cells by providing pro-apoptotic factors that are released from the mitochondrial inter-membranous space upon the induction of mitochondrial outer membrane permeabilization. This intrinsic death signaling pathway is the preferred mechanism employed by most anticancer compounds, and as such, resistance to drug-induced apoptosis is invariably associated with inhibition of mitochondrial death signaling network. The latter is a function of a balance between the pro- and the anti-apoptotic members of the Bcl-2 family. Bcl-2 is the prototype anti-apoptotic protein that localizes to the mitochondria and blocks the recruitment and activation of pro-apoptotic proteins, such as Bax, to the mitochondria. Recent Advances and Critical Issues: Recent evidence has highlighted a novel mechanism of anti-apoptotic activity of Bcl-2 in addition to its canonical activity in regulating mitochondrial outer membrane permeabilization. This novel activity is a function of cellular redox regulation, in particular, mitochondrial metabolism in cancer cells. Future Directions: Here we review the current state of our understanding of the death inhibitory activity of Bcl-2 and provide insight into the novel functional biology of this remarkable protein, which could have implications for designing innovative strategies to overcome the problem of drug resistance in the clinical settings. © Copyright 2011, Mary Ann Liebert, Inc. 2011. 2011 Journal Article http://hdl.handle.net/20.500.11937/51225 10.1089/ars.2010.3851 Mary Ann Liebert, Inc. Publishers restricted
spellingShingle Low, I.
Kang, J.
Pervaiz, Shazib
Bcl-2: A prime regulator of mitochondrial redox metabolism in cancer cells
title Bcl-2: A prime regulator of mitochondrial redox metabolism in cancer cells
title_full Bcl-2: A prime regulator of mitochondrial redox metabolism in cancer cells
title_fullStr Bcl-2: A prime regulator of mitochondrial redox metabolism in cancer cells
title_full_unstemmed Bcl-2: A prime regulator of mitochondrial redox metabolism in cancer cells
title_short Bcl-2: A prime regulator of mitochondrial redox metabolism in cancer cells
title_sort bcl-2: a prime regulator of mitochondrial redox metabolism in cancer cells
url http://hdl.handle.net/20.500.11937/51225