title: Analysis of the mechanism of radiation-induced upregulation of mitochondrial abundance in mouse fibroblasts.
abstract: Mitochondria strongly contribute to the maintenance of cellular integrity through various mechanisms, including oxidative adenosine triphosphate production and calcium homeostasis regulation. Therefore, proper regulation of the abundance, distribution and activity of mitochondria is crucial for the maintenance of cellular homeostasis. Previous studies have shown that ionizing radiation (IR) alters mitochondrial functions, suggesting that mitochondria are likely to be an important target of IR. Though IR reportedly influences cellular mitochondrial abundance, the mechanism remains largely unknown. In this study, we examined how IR influences mitochondrial abundance in mouse fibroblasts. When mouse NIH/3T3 cells were exposed to X-rays, a time-dependent increase was observed in mitochondrial DNA (mtDNA) and mitochondrial mass, indicating radiation-induced upregulation of mitochondrial abundance. Meanwhile, not only did we not observe a significant change in autophagic activity after irradiation, but in addition, IR hardly influenced the expression of two mitochondrial proteins, cytochrome c oxidase subunit IV and cytochrome c, or the mRNA expression of Polg, a component of DNA polymerase γ. We also observed that the expression of transcription factors involved in mitochondrial biogenesis was only marginally affected by IR. These data imply that radiation-induced upregulation of mitochondrial abundance is an event independent of macroautophagy and mitochondrial biogenesis. Furthermore, we found evidence that IR induced long-term cell cycle arrest and cellular senescence, indicating that these events are involved in regulating mitochondrial abundance. Considering the growing significance of mitochondria in cellular radioresponses, we believe the present study provides novel insights into understanding the effects of IR on mitochondria.
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamamori
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Sasagawa
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ichii
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Hiyoshi
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Bo
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kon
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Inanami
mesh_terms: D000818:Animals; D001343:Autophagy / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects; D016922:Cellular Senescence / Q000528:radiation effects; D004261:DNA Replication / Q000528:radiation effects; D004272:DNA, Mitochondrial / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000528:radiation effects; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000528:radiation effects* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism; D041681:NIH 3T3 Cells; D001678:Organelle Biogenesis; D015854:Up-Regulation / Q000528:radiation effects*; D014965:X-Rays
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins
keywords: cell cycle arrest; cellular radioresponse; cellular senescence; ionizing radiation; mitochondria; mitochondrial biogenesis