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

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Title: Inhibition of the mitochondrial fission protein dynamin-related protein 1 (Drp1) impairs mitochondrial fission and mitotic catastrophe after x-irradiation
Authors: Yamamori, Tohru Browse this author →KAKEN DB
Ike, Satoshi Browse this author
Bo, Tomoki Browse this author
Sasagawa, Tomoya Browse this author
Sakai, Yuri Browse this author
Suzuki, Motofumi Browse this author
Yamamoto, Kumiko Browse this author
Nagane, Masaki Browse this author
Yasui, Hironobu Browse this author →KAKEN DB
Inanami, Osamu Browse this author →KAKEN DB
Issue Date: 15-Dec-2015
Publisher: American Society for Cell Biology
Journal Title: Molecular Biology of the Cell
Volume: 26
Issue: 25
Start Page: 4607
End Page: 4617
Publisher DOI: 10.1091/mbc.E15-03-0181
Abstract: 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.
Rights: http://creativecommons.org/licenses/by-nc-sa/3.0
Type: article
URI: http://hdl.handle.net/2115/60342
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 山盛 徹

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