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Mitochondrial Autophagy in Aging

Research Project

Project/Area Number 19K23822
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0802:Biomedical structure and function and related fields
Research InstitutionNiigata University

Principal Investigator

Inoue Keiichi  新潟大学, 医歯学系, 特任助教 (30396981)

Project Period (FY) 2019-08-30 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsマイトファジー / 老化 / 線維芽細胞 / 遺伝子改変マウス / 細胞老化
Outline of Research at the Start

マイトファジーは、細胞の老化に関与すると考えられているが、そのメカニズムはは不明である。申請者は、マイトファジーが細胞老化を抑制していると考え、マウス培養細胞の老化モデルを用いて検証する。具体的には、①マイトファジーと細胞老化の相関、②マイトファジーの細胞老化に対する影響、を解析する。本研究では、マイトファジーによる細胞老化の制御機構を解明するとともに、老化や老年性疾患を抑制するターゲットを提示する。

Outline of Final Research Achievements

Mitophagy (autophagic degradation of mitochondria) is thought to be involved in aging process by degrading injured mitochondria. However, the relationship between mitophagy and aging and its mechanism remain unknown. The applicant believed that age-related changes in mitophagy activity regulate aging process, and verified it using mitophagy reporter mice and cells isolated from them. Specifically, (1) changes and correlations of mitophagy activity during the aging process, and (2) effects of mitophagy activity on aging will be analyzed. In this study, we elucidated the involvement of mitophagy in the aging process and aimed to present a target for suppressing senile diseases.

Academic Significance and Societal Importance of the Research Achievements

マイトファジー(ミトコンドリアのオートファジー分解)は、傷害を受けたミトコンドリアを分解する。老化にともない傷害されたミトコンドリアが増加することから、老化の過程においてマイトファジー活性は低下していると考えられてきた。しかしながらマイトファジーと老化の関連やそのメカニズムは不明である。本研究は、老化過程におけるマイトファジーの関わりを明らかにし、そのメカニズムをの一端を解明した。また現在の超高齢社会において、健康寿命を延伸するための治療法開発の標的として、マイトファジーの活性調節がその候補となりうることを明らかにした。

Report

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

    (11 results)

All 2021 2020 2019 Other

All Journal Article (9 results) (of which Peer Reviewed: 6 results,  Open Access: 4 results) Remarks (2 results)

  • [Journal Article] Mitophagy reporter mouse analysis reveals increased mitophagy activity in disuse‐induced muscle atrophy2021

    • Author(s)
      Yamashita Shun‐Ichi、Kyuuma Masanao、Inoue Keiichi、Hata Yuki、Kawada Ryu、Yamabi Masaki、Fujii Yasuyuki、Sakagami Junko、Fukuda Tomoyuki、Furukawa Kentaro、Tsukamoto Satoshi、Kanki Tomotake
    • Journal Title

      Journal of Cellular Physiology

      Volume: N/A Issue: 11 Pages: 7612-7624

    • DOI

      10.1002/jcp.30404

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CRISPR-activated patient fibroblasts for modeling of familial Alzheimer's disease2021

    • Author(s)
      Inoue Keiichi
    • Journal Title

      Neuroscience Research

      Volume: N/A Pages: 7-12

    • DOI

      10.1016/j.neures.2021.03.008

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association and dissociation between the mitochondrial Far complex and Atg32 regulate mitophagy2020

    • Author(s)
      Innokentev Aleksei、Furukawa Kentaro、Fukuda Tomoyuki、Saigusa Tetsu、Inoue Keiichi、Yamashita Shun-ichi、Kanki Tomotake
    • Journal Title

      eLife

      Volume: 9

    • DOI

      10.7554/elife.63694

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Atg43 tethers isolation membranes to mitochondria to promote starvation-induced mitophagy in fission yeast2020

    • Author(s)
      Fukuda Tomoyuki、Ebi Yuki、Saigusa Tetsu、Furukawa Kentaro、Yamashita Shun-ichi、Inoue Keiichi、Kobayashi Daiki、Yoshida Yutaka、Kanki Tomotake
    • Journal Title

      eLife

      Volume: 9

    • DOI

      10.7554/elife.61245

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] クリスパー転写活性化によるアルツハイマー病線維芽細胞モデルの作製2020

    • Author(s)
      井上敬一
    • Journal Title

      CLINICAL NEUROSCIENCE

      Volume: 38 Pages: 1052-1054

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Gemcitabine induces Parkin-independent mitophagy through mitochondrial-resident E3 ligase MUL1-mediated stabilization of PINK1.2020

    • Author(s)
      Igarashi R, Yamashita SI, Yamashita T, Inoue K, Fukuda T, Fukuchi T, Kanki T.
    • Journal Title

      Sci Rep.

      Volume: 10(1) Issue: 1 Pages: 1465-1465

    • DOI

      10.1038/s41598-020-58315-w

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glaucoma-Associated Mutations in the Optineurin Gene Have Limited Impact on Parkin-Dependent Mitophagy.2019

    • Author(s)
      Chernyshova K, Inoue K, Yamashita SI, Fukuchi T, Kanki T.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 60(10) Issue: 10 Pages: 3625-3635

    • DOI

      10.1167/iovs.19-27184

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 哺乳類におけるミトコンドリアオートファジーの分子機構2019

    • Author(s)
      井上敬一、山下俊一、神吉智丈
    • Journal Title

      実験医学増刊

      Volume: 37 Pages: 58-64

    • Related Report
      2019 Research-status Report
  • [Journal Article] ミトコンドリアオートファジーと老化との関連2019

    • Author(s)
      神吉智丈、井上敬一
    • Journal Title

      FRAGRANCE JOURNAL

      Volume: 47 Pages: 36-39

    • Related Report
      2019 Research-status Report
  • [Remarks] 所属研究室Webサイト

    • URL

      https://www.med.niigata-u.ac.jp/mit/

    • Related Report
      2020 Annual Research Report
  • [Remarks] Researchmap

    • URL

      https://researchmap.jp/kinoue12

    • Related Report
      2020 Annual Research Report

URL: 

Published: 2019-09-03   Modified: 2025-01-30  

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