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Inhibition of the mitochondrial fission protein dynamin-related protein 1 (Drp1) impairs mitochondrial fission and mitotic catastrophe after x-irradiation

Accumulating evidence suggests that mitochondrial dynamics is crucial for the maintenance of cellular quality control and function in response to various stresses. However, the role of mitochondrial dynamics in cellular responses to ionizing radiation (IR) is still largely unknown. In this study, we...

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Autores principales: Yamamori, Tohru, Ike, Satoshi, Bo, Tomoki, Sasagawa, Tomoya, Sakai, Yuri, Suzuki, Motofumi, Yamamoto, Kumiko, Nagane, Masaki, Yasui, Hironobu, Inanami, Osamu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678018/
https://www.ncbi.nlm.nih.gov/pubmed/26466676
http://dx.doi.org/10.1091/mbc.E15-03-0181
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author Yamamori, Tohru
Ike, Satoshi
Bo, Tomoki
Sasagawa, Tomoya
Sakai, Yuri
Suzuki, Motofumi
Yamamoto, Kumiko
Nagane, Masaki
Yasui, Hironobu
Inanami, Osamu
author_facet Yamamori, Tohru
Ike, Satoshi
Bo, Tomoki
Sasagawa, Tomoya
Sakai, Yuri
Suzuki, Motofumi
Yamamoto, Kumiko
Nagane, Masaki
Yasui, Hironobu
Inanami, Osamu
author_sort Yamamori, Tohru
collection PubMed
description Accumulating evidence suggests that mitochondrial dynamics is crucial for the maintenance of cellular quality control and function in response to various stresses. However, the role of mitochondrial dynamics in cellular responses to ionizing radiation (IR) is still largely unknown. In this study, we provide evidence that IR triggers mitochondrial fission mediated by the mitochondrial fission protein dynamin-related protein 1 (Drp1). We also show IR-induced mitotic catastrophe (MC), which is a type of cell death associated with defective mitosis, and aberrant centrosome amplification in mouse embryonic fibroblasts (MEFs). These are attenuated by genetic or pharmacological inhibition of Drp1. Whereas radiation-induced aberrant centrosome amplification and MC are suppressed by the inhibition of Plk1 and CDK2 in wild-type MEFs, the inhibition of these kinases is ineffective in Drp1-deficient MEFs. Furthermore, the cyclin B1 level after irradiation is significantly higher throughout the time course in Drp1-deficient MEFs than in wild-type MEFs, implying that Drp1 is involved in the regulation of cyclin B1 level. These findings strongly suggest that Drp1 plays an important role in determining the fate of cells after irradiation via the regulation of mitochondrial dynamics.
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spelling pubmed-46780182016-03-01 Inhibition of the mitochondrial fission protein dynamin-related protein 1 (Drp1) impairs mitochondrial fission and mitotic catastrophe after x-irradiation Yamamori, Tohru Ike, Satoshi Bo, Tomoki Sasagawa, Tomoya Sakai, Yuri Suzuki, Motofumi Yamamoto, Kumiko Nagane, Masaki Yasui, Hironobu Inanami, Osamu Mol Biol Cell Articles Accumulating evidence suggests that mitochondrial dynamics is crucial for the maintenance of cellular quality control and function in response to various stresses. However, the role of mitochondrial dynamics in cellular responses to ionizing radiation (IR) is still largely unknown. In this study, we provide evidence that IR triggers mitochondrial fission mediated by the mitochondrial fission protein dynamin-related protein 1 (Drp1). We also show IR-induced mitotic catastrophe (MC), which is a type of cell death associated with defective mitosis, and aberrant centrosome amplification in mouse embryonic fibroblasts (MEFs). These are attenuated by genetic or pharmacological inhibition of Drp1. Whereas radiation-induced aberrant centrosome amplification and MC are suppressed by the inhibition of Plk1 and CDK2 in wild-type MEFs, the inhibition of these kinases is ineffective in Drp1-deficient MEFs. Furthermore, the cyclin B1 level after irradiation is significantly higher throughout the time course in Drp1-deficient MEFs than in wild-type MEFs, implying that Drp1 is involved in the regulation of cyclin B1 level. These findings strongly suggest that Drp1 plays an important role in determining the fate of cells after irradiation via the regulation of mitochondrial dynamics. The American Society for Cell Biology 2015-12-15 /pmc/articles/PMC4678018/ /pubmed/26466676 http://dx.doi.org/10.1091/mbc.E15-03-0181 Text en © 2015 Yamamori et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Yamamori, Tohru
Ike, Satoshi
Bo, Tomoki
Sasagawa, Tomoya
Sakai, Yuri
Suzuki, Motofumi
Yamamoto, Kumiko
Nagane, Masaki
Yasui, Hironobu
Inanami, Osamu
Inhibition of the mitochondrial fission protein dynamin-related protein 1 (Drp1) impairs mitochondrial fission and mitotic catastrophe after x-irradiation
title Inhibition of the mitochondrial fission protein dynamin-related protein 1 (Drp1) impairs mitochondrial fission and mitotic catastrophe after x-irradiation
title_full Inhibition of the mitochondrial fission protein dynamin-related protein 1 (Drp1) impairs mitochondrial fission and mitotic catastrophe after x-irradiation
title_fullStr Inhibition of the mitochondrial fission protein dynamin-related protein 1 (Drp1) impairs mitochondrial fission and mitotic catastrophe after x-irradiation
title_full_unstemmed Inhibition of the mitochondrial fission protein dynamin-related protein 1 (Drp1) impairs mitochondrial fission and mitotic catastrophe after x-irradiation
title_short Inhibition of the mitochondrial fission protein dynamin-related protein 1 (Drp1) impairs mitochondrial fission and mitotic catastrophe after x-irradiation
title_sort inhibition of the mitochondrial fission protein dynamin-related protein 1 (drp1) impairs mitochondrial fission and mitotic catastrophe after x-irradiation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678018/
https://www.ncbi.nlm.nih.gov/pubmed/26466676
http://dx.doi.org/10.1091/mbc.E15-03-0181
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