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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Bibliographic Details
Published in:Molecular biology of the cell 2015-12, Vol.26 (25), p.4607-4617
Main Authors: Yamamori, Tohru, Ike, Satoshi, Bo, Tomoki, Sasagawa, Tomoya, Sakai, Yuri, Suzuki, Motofumi, Yamamoto, Kumiko, Nagane, Masaki, Yasui, Hironobu, Inanami, Osamu
Format: Article
Language:English
Subjects:
Animals
Apoptosis - radiation effects
Centrosome - radiation effects
Cyclin B1 - genetics
Dynamins - genetics
Fibroblasts - radiation effects
Mice
Mitochondria - genetics
Mitochondria - radiation effects
Mitochondrial Dynamics - genetics
Mitochondrial Dynamics - radiation effects
Mitosis - radiation effects
X-Rays
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Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.e15-03-0181