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Elucidating role of GTP hydrolysis in GTPase-driven mitochondrial membrane fusion

Research Project

Project/Area Number 18K06096
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43020:Structural biochemistry-related
Research InstitutionKurume University

Principal Investigator

Ban Tadato  久留米大学, 分子生命科学研究所, 講師 (00579667)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsミトコンドリア / 膜融合 / GTPase / 膜タンパク質 / 脂質膜 / リポソーム / カルジオリピン / 試験内再構成 / Mitofusin / バキュロウイルス発現 / カイコ / OPA1 / カルジリピン
Outline of Final Research Achievements

Mitochondria are highly dynamic organelles, which move and fuse to regulate their shape, size and fundamental functions. The dynamin-related large GTPases has been reported to play a central role in mitochondrial fusion. However, how theses GTPases mediated mitochondrial fusion remains unclear. To address the molecular mechanisms underlying mitochondrial fusion, we have been developed in vitro assays to analysis the membrane fusion reaction using highly purified recombinant proteins and model membranes. From a series of in vitro membrane fusion and binding analysis, we found that short form OPA1 bridges the opposite membrane in a mitochondrial specific lipid cardiolipin. In addition to in vitro assays, we have developed the methods to purify large amount of recombinant OPA1 for the structural analysis.

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリアは、細胞内のエネルギーを生産する以外にも、細胞死の制御やホルモン、脂質などの生体分子の代謝に機能する多彩な細胞小器官である。ミトコンドリア膜融合は、この多彩な機能を支える必須の過程であり、その分子機構を理解することは、生命の成り立ちを理解する上でも重要である。近年、ミトコンドリア融合の不全が、アルツハイマー病やパーキンソン病といった神経変性疾患や、がん、糖尿病の発症に深く関連し、ミトコンドリアに着目した予防・治療法が注目されている。本研究から得られる知見は、ミトコンドリアの関与するさまざまな病態の治療や予防に向けて、広く社会に還元できるものであると考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (14 results)

All 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (3 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results) Book (1 results)

  • [Int'l Joint Research] カリフォルニア工科大学(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] カリフォルニア工科大学(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Analysis of Mitochondrial Membrane Fusion GTPase OPA1 Expressed by the Expression System2020

    • Author(s)
      Ban Tadato、Ishihara Naotada
    • Journal Title

      Methods in Molecular Biology

      Volume: 2159 Pages: 115-127

    • DOI

      10.1007/978-1-0716-0676-6_9

    • ISBN
      9781071606759, 9781071606766
    • Related Report
      2020 Annual Research Report
  • [Journal Article] Regulation of mitochondrial inner-membrane fusion by OPA1 and cardiolipin2019

    • Author(s)
      植田 依里, 伴 匡人, 石原 直忠
    • Journal Title

      生化学

      Volume: 91 Issue: 2 Pages: 268-271

    • DOI

      10.14952/SEIKAGAKU.2019.910268

    • NAID

      40021942535

    • ISSN
      0037-1017
    • Year and Date
      2019-04-25
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relationship between OPA1 and cardiolipin in mitochondrial inner-membrane fusion2018

    • Author(s)
      Ban Tadato、Kohno Hiroto、Ishihara Takaya、Ishihara Naotada
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Bioenergetics

      Volume: 1859 Issue: 9 Pages: 951-957

    • DOI

      10.1016/j.bbabio.2018.05.016

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] ミトコンドリア膜融合GTPase OPA1による膜融合機構の解析2019

    • Author(s)
      伴 匡人、石原直忠
    • Organizer
      第71回日本細胞生物学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 再構成実験によるミトコンドリア内膜融合機構の解明2019

    • Author(s)
      伴 匡人
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Heterotypic action between OPA1 and cardiolipin in mitochondrial fusion2018

    • Author(s)
      Tadato Ban, Naotada Ishihara
    • Organizer
      The1st International Mitochondria Meeting for Young Scientist
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Elucidating the mechanism of selective mitochondrial fusion by OPA1 and cardiolipin2018

    • Author(s)
      Tadato Ban, Naotada Ishihara
    • Organizer
      第70回日本細胞生物学会(日本発生生物学会合同大会)
    • Related Report
      2018 Research-status Report
  • [Presentation] 膜融合GTPase OPA1によるミトコンドリア膜融合機構の解明2018

    • Author(s)
      伴 匡人、石原 直忠
    • Organizer
      平成30年度 日本生化学会 九州支部例会
    • Related Report
      2018 Research-status Report
  • [Presentation] ミトコンドリア膜融合ダイナミクスの分子機構2018

    • Author(s)
      伴 匡人、石原 直忠
    • Organizer
      レドックス第170委員会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 膜融合GTPaseによるミトコンドリア膜融合メカニズム2018

    • Author(s)
      伴 匡人、石原 直忠
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Elucidating molecular mechanism of OPA1 mediated mitochondrial inner membrane fusion2018

    • Author(s)
      Tadato Ban, Naotada Ishihara
    • Organizer
      International Symposium on Mitochondrial Biology and Disease
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] Silkworm Biofactory : Silk to Biology, Chapter 11 "Expression and Purification of Mitochondrial Membrane Protein OPA1 for Reconstitution of Membrane Fusion"2018

    • Author(s)
      Tadato Ban, Naotada Ishihara
    • Total Pages
      11
    • Publisher
      CRC Press
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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