量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
Thank you very much for using our website. On the 11th of March 2019, this site was moved from our own network server to the JAIRO Cloud network server. If you previously bookmarked this site, that bookmark will no longer work. We would be grateful if you could bookmark the website again. Thank you very much for your understanding and cooperation.
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.
雑誌名
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
Fragmentation level determines mitochondrial damage response and subsequently the fate of cancer cells exposed to carbon ions.
