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The mechanism of Drp1-dependent mitochondrial fission

Research Project

Project/Area Number 24657138
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Cell biology
Research InstitutionKyushu University

Principal Investigator

MIHARA Katsuyoshi  九州大学, 医学(系)研究科(研究院), 名誉教授 (40029963)

Co-Investigator(Kenkyū-buntansha) 岡 敏彦  九州大学, 医学研究院, 准教授 (40263321)
大寺 秀典  九州大学, 医学研究院, 助教 (40380612)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsミトコンドリア / ミトコンドリア分裂 / ミトコンドリア融合 / Drp1 / Mff / Mid49 / Mid51 / DRP1 / Fis1 / Mfn1 / Mfn2 / ミトコンドリア動態 / hFis1
Research Abstract

Mitochondria participate in a variety of physiologic processes such as the ATP poroduction and apoptosis. Mitochondria dynamically change morphology through fusion and fission and high MW GTPases Mfn1 and Mfn2 of outer membrane and OPA1 of inner membrane are involved in fusion, whereas cytoplasimic Drp1 regulates fission. Here, (1) Since outer membrane proteins Mff, Mid49 and Mid51 function as the Drp1 receptor, we analyzed relative importance of these receptors and found that Mff as the major Drp1 receptor. (2) We have generated Mff-KO mice; they were embryonic lethal (E6.5). Consideing that Drp1-KO mice are lethal at E12.5, Mff seems to have important developmental function in addition to the Drp1-receptor function. Furhtermore, we have demonstrated that (3) Drp1 is involved in segregation of mitochondrial nucleoids, Drp1 is esssential for making correctly arranged heart mucle fibers, and konckout of liver Drp1 induced NASH phenotype in high fat diet-fed rats by the ER stress.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (25 results)

All 2013 2012 2011 Other

All Journal Article (11 results) (of which Peer Reviewed: 6 results) Presentation (13 results) (of which Invited: 5 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Dynamics of nucleoid structure regulated by mitochondrial fission contributes to cristae reformation and release of cytochrome c2013

    • Author(s)
      R. Ban-Ishihara, T. Ishihara, N. Sasaki, K. Mihara and N. Ishihara
    • Journal Title

      Pros. Natl. Acad. Sci. USA

      Volume: 110 Pages: 11863-11868

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Journal Article] New insights into the function and regulation of mitochondrial fission2013

    • Author(s)
      H. Otera, N. Ishihara, and K. Mihara.
    • Journal Title

      Biochim. Biophys. Acta

      Volume: 1833(5) Pages: 1256-1268

    • Related Report
      2013 Final Research Report
  • [Journal Article] Fis1 acts as mitochondrial recruitment of TBC1D15 that involved in regulation of mitochondrial morphology2013

    • Author(s)
      K. Onoue et al.
    • Journal Title

      J. Cell Sci.

      Volume: 126 Issue: 1 Pages: 176-186

    • DOI

      10.1242/jcs.111211

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] New insights into the function and regulation of mitochondrial fission2013

    • Author(s)
      H. Otera, N. Ishihara, and K. Mihara
    • Journal Title

      Biochim. Biophys. Acta Molecular Cell Biology

      Volume: 1833 Pages: 1256-1268

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fis1 acts as mitochondrial recruitment factor for TBC1D15 that involved in regulation of mitochondrial morphology2013

    • Author(s)
      K. Onoue, A. Jofuku, R. Ban-Ishihara, T. Ishihara, M. Maeda, T. Koshiba, T. Itoh, M. Fukuda, H. Otera, T. Oka, H. Takano, N. Mizushima, K. Mihara and N. Ishihara
    • Journal Title

      J. Cell Sci.

      Volume: 126 Pages: 176-185

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New insights into the function and regulation of mitochondrial fission2013

    • Author(s)
      H. Otera, N. Ishihara, and K. Mihara
    • Journal Title

      BBA Mol. Cell. Res.

      Volume: 1833 Pages: 1256-1268

    • Related Report
      2012 Research-status Report
  • [Journal Article] PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria2012

    • Author(s)
      尾勝圭
    • Journal Title

      Nature Communications

      Volume: 3 Issue: 1 Pages: 1016-1016

    • DOI

      10.1038/ncomms2016

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation and physiologic function of GTPases in mitochondrial fusion and fission in mammals2012

    • Author(s)
      N. Ishihara, H. Otera, T. Oka, and K, Mihara
    • Journal Title

      Invited Forum Review Article. Antioxid. Redox Signal

      Volume: 17(PMID : 22871170) Pages: 1-11

    • Related Report
      2013 Final Research Report
  • [Journal Article] Mitochondrial dynamics : functional link with apoptosis2012

    • Author(s)
      H.Otera, K.Mihara
    • Journal Title

      International J.Cell Biol.

      Volume: (Invited review article)(in press) Pages: 1-10

    • DOI

      10.1155/2012/821676

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation and physiologic functions of GTPases in mitochondrial fusion and fission in mammals2012

    • Author(s)
      Ishihara, N., H. Otera, T. Oka, and K. Mihara
    • Journal Title

      Antioxidant & Redox Signaling

      Volume: ー Issue: 4 Pages: 389-399

    • DOI

      10.1089/ars.2012.4830

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Discovery of the membrane receptor for mitochondrial fission GTPase Drp12011

    • Author(s)
      H. Otera and K. Mihara
    • Journal Title

      Invited Review Article. Small GTPases

      Volume: 2(3) Pages: 167-172

    • Related Report
      2013 Final Research Report
  • [Presentation] The Mechanism and physiological Significance of Drp1-dependent Mitochondrial Fission in Mammals2013

    • Organizer
      The 2013 International Symposium on Mitochondrial Dynamics in Translational Medicine & 2013 Annual Meeting of Mitochondrial Research and Medicine (TSMRM)
    • Place of Presentation
      Taipei Medical University, Taiwan(Invited Talk)
    • Year and Date
      2013-09-07
    • Related Report
      2013 Final Research Report
  • [Presentation] Mechanism and Regulation of Mitochondrial Fission in Mammalian Cells2013

    • Author(s)
      K. Mihara
    • Organizer
      The International Symposium on Mitochondria
    • Place of Presentation
      Roppongi, Tokyo, Japan(Invited Talk)
    • Related Report
      2013 Final Research Report
  • [Presentation] Mechanism and Physiologic Significance of Drp1-dependent Mitochondrial Fission in Mammals2013

    • Author(s)
      K. Mihara
    • Organizer
      Plenary Lecture in The 4th International Symposium on Dynamics of Mitochondria : from Molecular Mechanisms to Physiological Functions and Diseases
    • Place of Presentation
      Okinawa
    • Related Report
      2013 Final Research Report
  • [Presentation] Mechanism and Regulation of Mitochondrial Fission in Mammalian Cells2013

    • Author(s)
      K. Mihara
    • Organizer
      International Symposium on Mitochondria 2013
    • Place of Presentation
      Roppongi, Tokyo, Japan
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Mechanism and Physiological Function of Mitochondrial Fission in Mammalian Cells2013

    • Author(s)
      K. Mihara
    • Organizer
      4th International Symposium on Dynamics of Mitochondria: from molecular mechanisms to physiological functions and diseases
    • Place of Presentation
      Okinawa, Japan
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ミトコンドリア分裂の制御機構とその障害2012

    • Author(s)
      三原勝芳
    • Organizer
      The 12th Conference of Japanese Society of Mitochondrial Research and Medicine (J-Mit)
    • Place of Presentation
      筑波大学(特別講演)
    • Year and Date
      2012-12-20
    • Related Report
      2013 Final Research Report
  • [Presentation] 細胞の生と死をつかさどる小器官ミトコンドリア-機能、形成、動態とその障害2012

    • Author(s)
      三原勝芳
    • Organizer
      独創的発想に富む科学者育成プログラム「出る杭を伸ばすヘリックスプロジェクト」採択事業|七人の侍による記念講演会
    • Place of Presentation
      秋田ビューホテル
    • Year and Date
      2012-10-24
    • Related Report
      2013 Final Research Report
  • [Presentation] ミトコンドリア融合・分裂の分子機構と生理機能2012

    • Author(s)
      三原勝芳
    • Organizer
      グローバルCOEプログラム理医連携特別講演会–独創的研究の世界発信を続ける「七人の侍」–
    • Place of Presentation
      九州大学コラボステーション1視聴覚ホール
    • Year and Date
      2012-02-29
    • Related Report
      2013 Final Research Report
  • [Presentation] The mechanism and physiological significance of Drp1-dependent mitochondrial fission in mammals2012

    • Author(s)
      K. Mihara
    • Organizer
      The 9th Conference of the Asian Society of Mitochondrial Research and Medicine & The 5th Conference of Chinese Society of Mitochondrial Research and Medicine
    • Place of Presentation
      (Invited talk)
    • Related Report
      2013 Final Research Report
  • [Presentation] 特別講演「ミトコンドリア分裂の制御機構とその障害」2012

    • Author(s)
      三原 勝芳
    • Organizer
      第12回日本ミトコンドリア学会
    • Place of Presentation
      筑波大学
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Mechanism and physiological significance of Drp1-dependent mitochondrial fission in mammals.2012

    • Author(s)
      K. Mihara
    • Organizer
      Asian Society of Mitochondrial Research and Medicine & Conference of Chinese Society of Mitochondrial Research and Medicine
    • Place of Presentation
      Beijin
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 「細胞の生と死をつかさどる小器官ミトコンドリア-機能、形成、動態と その障害2012

    • Author(s)
      三原勝芳
    • Organizer
      独創的発想に富む科学者育成プログラム「出る杭を伸ばすヘリックすプロジェクト」採択事業|七人の侍による記念講演会
    • Place of Presentation
      秋田市
    • Related Report
      2012 Research-status Report
  • [Presentation] The Mechanism and physiological Significance of Drp1-dependent Mitochondrial Fission in Mammals

    • Author(s)
      K. Mihara
    • Organizer
      2013 International Symposium on Mitochondrial Dynamics in Translational Medicine & 2013 Annual Meeting of Mitochondrial Reseach and Medicine (TSMRM)
    • Place of Presentation
      Taipei Medical University, Taiwan
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Patent(Industrial Property Rights)] Drp1欠損非ヒトほ乳動物2013

    • Inventor(s)
      三原勝芳、石原直忠
    • Industrial Property Rights Holder
      株式会社ジェンテック
    • Industrial Property Number
      2007-298224
    • Acquisition Date
      2013-07-05
    • Related Report
      2013 Final Research Report
    • Overseas

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Published: 2013-05-31   Modified: 2019-07-29  

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