@article{oai:repo.qst.go.jp:00049291, author = {Jin, Xiaodong and Zheng, Xiaogang and Li, Feifei and Liu, Bingtao and Li, Hongbin and Hirayama, Ryoichi and Li, Ping and Liu, Xiongxiong and Shen, Guosheng and Li, Qiang and Jin, Xiaodong and Hirayama, Ryoichi and Li, Ping and Xiongxiong, Liu and Li, Qiang}, issue = {1}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, month = {Oct}, note = {OBJECTIVES: Although mitochondria are known to play an important role in radiation-induced cellular damage response, the mechanisms of how radiation elicits mitochondrial responses are largely unknown. MATERIALS AND METHODS: Human cervical cancer cell line HeLa and human breast cancer cell lines MCF-7 and MDA-MB-231 were irradiated with high LET carbon ions at low (0.5 Gy) and high (3 Gy) doses. Mitochondrial functions, dynamics, mitophagy, intrinsic apoptosis and total apoptosis, and survival fraction were investigated after irradiation. RESULTS: We found that carbon ions irradiation induced two different mitochondrial morphological changes and corresponding responses in cancer cells. Cells exposed to carbon ions of 0.5 Gy exhibited only modestly truncated mitochondria, and subsequently damaged mitochondria could be eliminated through mitophagy. In contrast, mitochondria within cells insulted by 3 Gy radiation split into punctate and clustered ones, which were associated with apoptotic cell death afterward. Inhibition of mitochondrial fission by Drp1 or FIS1 knockdown or with the Drp1 inhibitor mdivi-1 suppressed mitophagy and potentiated apoptosis after irradiation at 0.5 Gy. However, inhibiting fission led to mitophagy and increased cell survival when cells were irradiated with carbon ions at 3 Gy. CONCLUSION: We proposed a stress response model to provide a mechanistic explanation for the mitochondrial damage response to high-LET carbon ions.}, pages = {75--83}, title = {Fragmentation level determines mitochondrial damage response and subsequently the fate of cancer cells exposed to carbon ions.}, volume = {129}, year = {2018} }