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Development of quantitative measurement method of ATP production rate in mitochondria in mouse

Research Project

Project/Area Number 19K22513
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 48:Biomedical structure and function and related fields
Research InstitutionNational Cardiovascular Center Research Institute (2020-2021)
Kyoto University (2019)

Principal Investigator

Yamamoto Masamichi  国立研究開発法人国立循環器病研究センター, 研究所, 特任部長 (70423150)

Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsアデノシン三リン酸 / エネルギー代謝 / イメージング / ミトコンドリア / マウス / 可視化
Outline of Research at the Start

本研究ではイメージング技術を用いてマウス生体内全細胞で臓器から細胞レベルに至るまで、ミトコンドリアのエネルギー産生機能を直接評価できる、非侵襲的かつ定量的に計測するシステムを開発する事を目的とする。これにより生体内のエネルギー代謝反応の動態や、エネルギー代謝異常が報告されている心疾患・精神疾患・神経変性疾患などのミトコンドリアを基軸としたメカニズム解明への適応が期待される。

Outline of Final Research Achievements

There is a great need in the life science field for "a robust technology that can quantitatively measure the rate of ATP (adenosine triphosphate) production in mitochondria in vivo," but there has been no core technology to meet this need. The reason for this is that it is not possible to directly measure the amount of ATP in mitochondria.
In this study, we created a new ATP sensor protein, CR-ATeam, as a technology to measure ATP dynamics in mitochondria by experimenting with various fluorescent proteins that improve the brightness value of ATP. We also tried to generate mice by using various constructs. As a result, we succeeded in generating a new mouse that expresses ATeam in the mitochondrial matrix.

Academic Significance and Societal Importance of the Research Achievements

高輝度のATPセンサー蛍光タンパク質であるCR-ATeamが作成され、低発現量でATP動態をFRET変化として計測できるプローブができた。
また、世界で初めて、ミトコンドリアマトリックス内で産生されるATP動態を生体内で計測できるマウスを作出した。これにより、生体内のミトコンドリア内ATP動態をin vitroだけでなくin vivoでも定量的に解析できるようになる。このマウスを用いれば、様々な疾患評価だけでなく薬剤評価などへも応用できると期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (6 results)

All 2022 2021

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

  • [Journal Article] Osteoclasts adapt to physioxia perturbation through DNA demethylation2021

    • Author(s)
      Nishikawa Keizo、Seno Shigeto、Yoshihara Toshitada、Narazaki Ayako、Sugiura Yuki、Shimizu Reito、Kikuta Junichi、Sakaguchi Reiko、Suzuki Norio、Takeda Norihiko、Semba Hiroaki、Yamamoto Masamichi、et al
    • Journal Title

      EMBO reports

      Volume: 22 Issue: 12 Pages: 53035-53035

    • DOI

      10.15252/embr.202153035

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Two‐photon AMPK and ATP imaging reveals the bias between rods and cones in glycolysis utility2021

    • Author(s)
      He Jiazhou、Yamamoto Masamichi、Sumiyama Kenta、Konagaya Yumi、Terai Kenta、Matsuda Michiyuki、Sato Shinya
    • Journal Title

      The FASEB Journal

      Volume: 35 Issue: 9

    • DOI

      10.1096/fj.202101121r

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rostro-caudal different energy metabolism leading to differences in degeneration in spinal cord injury2021

    • Author(s)
      Ohnishi Yuichiro、Yamamoto Masamichi、Sugiura Yuki、Setoyama Daiki、Kishima Haruhiko
    • Journal Title

      Brain Communications

      Volume: 3 Issue: 2

    • DOI

      10.1093/braincomms/fcab058

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] マウス生体内におけるATP動態の可視化2022

    • Author(s)
      山本正道
    • Organizer
      第99回日本生理学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] マウス生体内におけるATP動態の可視化と応用2021

    • Author(s)
      山本正道
    • Organizer
      第94回 生化学学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] マウス生体内におけるATP動態の可視化と応用2021

    • Author(s)
      山本正道
    • Organizer
      第147回 関西実験動物研究会
    • Related Report
      2021 Annual Research Report
    • Invited

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Published: 2019-07-04   Modified: 2023-01-30  

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