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Elucidation of the relationship of DNA lesion / DNA damage response and changes in mitochondrial activity

Research Project

Project/Area Number 19K21563
Project/Area Number (Other) 18H06501 (2018)
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund (2019)
Single-year Grants (2018)
Review Section 1101:Environmental analyses and evaluation, environmental conservation measure and related fields
Research InstitutionNational Institutes for Quantum and Radiological Science and Technology

Principal Investigator

Kaminaga Kiichi  国立研究開発法人量子科学技術研究開発機構, 量子生命科学領域, 博士研究員(任常) (90825176)

Project Period (FY) 2018-08-24 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsミトコンドリア / 放射線影響 / X線マイクロビーム / 細胞周期 / Fucci / マイクロビーム / ライブセルイメージング
Outline of Research at the Start

X線の生物影響を明らかにする上で細胞小器官へ影響を解明していく必要がある。本研究では特にミトコンドリアに対する放射線影響に着目し、ミトコンドリア活性とミトコンドリア量がX線のダメージによってどのように変化するのか、さらに細胞内部位特異的なX線照射やDNA損傷修復タンパク質の阻害剤を用いることで、DNA損傷とミトコンドリア活性・量変化の関連性を明らかにすることを目的とする。これにより外部ストレスに対する細胞小器官を含めた細胞応答の一端を明らかにできると期待される。

Outline of Final Research Achievements

The effects of ionizing radiation on organelles are largely unknown, and the effects on mitochondria which take on the most of ATP production are important for assessing the radiation effects. In this study, in order to clarify the relationship between DNA damage / DNA damage response and changes in mitochondrial mass and activity, X-ray microbeam was used to irradiate only the cell nucleus and cytoplasm. The chronological changes of mitochondrial mass and activity were measured by JC-1 staining. As a result, several days after irradiation, it was clarified that the mass of mitochondria was increased by nuclear irradiation and decreased by cytoplasmic irradiation. At this time, irradiation site-specific change was not observed in the mitochondrial membrane potential. This may suggest that the possibility of increase of mitochondrial mass was caused by DNA damage and damage response.

Academic Significance and Societal Importance of the Research Achievements

本研究は細胞核への限定的なX線照射によってもミトコンドリア量増加が誘発されることを明らかにした。ミトコンドリア量の増加はDNA損傷応答に必要なATPの産生量を増加させると同時に、活性酸素種の生成も増加するため、正・負両面の影響を細胞に与える可能性があり、さらに詳細な検討が必要である。また、オルガネラが直接放射線のヒットを受けない可能性がある低線量被ばくにおいても、核に放射線がヒットした場合にはDNA損傷によりオルガネラへ何らかの影響が誘発される可能性を示唆しており、ミトコンドリア以外のオルガネラへの影響を解明していく必要性を示唆すると考えられる。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • Research Products

    (6 results)

All 2019 2018

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] High-precision microbeam radiotherapy reveals testicular tissue-sparing effects for male fertility preservation2019

    • Author(s)
      Fukunaga, Hisanori Kaminaga, Kiichi Sato, Takuya Butterworth, Karl T. Watanabe, Ritsuko Usami, Noriko Ogawa, Takehiko Yokoya, Akinari Prise, Kevin M.
    • Journal Title

      Scientific Reports

      Volume: 9(1) Issue: 1 Pages: 12618-12618

    • DOI

      10.1038/s41598-019-48772-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MITOCHONDRIAL MEMBRANE POTENTIAL, MORPHOLOGY AND ATP PRODUCTION IN MAMMALIAN CELLS EXPOSED TO X-RAYS2019

    • Author(s)
      Hamada, R. Kaminaga, K. Suzuki, K. Yokoya, A.
    • Journal Title

      Radiation protection dosimetry

      Volume: 183(1-2) Issue: 1-2 Pages: 79-83

    • DOI

      10.1093/rpd/ncy254

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Visualization of the DNA repair process in mammalian cells transfected with EGFP-expressing plasmid DNA after exposure to X-rays in vitro2018

    • Author(s)
      Hiroki Nakaue, Yui Obata, Kiichi Kaminaga, Nobuyoshi Akimitsu, Akinari Yokoya
    • Journal Title

      Radiation Protection Dosimetry

      Volume: NCY241 Issue: 1-2 Pages: 1-5

    • DOI

      10.1093/rpd/ncy241

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] Trial for Real-Time Observation of Temperature in Mouse Fertilized Eggs using Fluorescent Nano-diamond2019

    • Author(s)
      Kiichi Kaminaga, Satoshi Tsukamoto, Ryutaro Aizawa, Takahiro Fujisaku, Akinari Yokoya, Shizuko Kaminuma, Masahiro Shirakawa and Ryuji Igarashi
    • Organizer
      3rd QST International Symposium "Quantum Life Science"
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Trial for Real-Time Observation of Temperature in Mouse Fertilized Eggs using Fluorescent Nano-diamond2019

    • Author(s)
      Kiichi Kaminaga, Satoshi Tsukamoto, Ryutaro Aizawa, Takahiro Fujisaku, Akinari Yokoya, Shizuko Kaminuma, Masahiro Shirakawa and Ryuji Igarashi
    • Organizer
      The 2nd International Forum on Quantum Metrology and Sensing(IFQMS)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] X線マイクロビームと蛍光ナノダイヤモンドを用いた放射線によるミトコンドリアへの影響解明にむけて2018

    • Author(s)
      神長輝一、寺田大紀、藤咲貴大、白川昌宏、五十嵐龍治、横谷明徳
    • Organizer
      日本ミトコンドリア学会 第18回年会
    • Related Report
      2018 Annual Research Report

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Published: 2018-08-27   Modified: 2024-03-26  

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