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Targeting mechanism of Drpl to mitochondrial fission sites

Research Project

Project/Area Number 21770214
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

OTERA Hidenori  Kyushu University, 医学研究院, 助教 (40380612)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords生体膜 / ミトコンドリア / 高分子量GTPase / 膜ダイナミズム / アポトーシス
Research Abstract

Cytoplasmic dynamin-related GTPase Drp1 is recruited to mitochondria and mediates mitochondrial fission. Although mitochondrial outer membrane (MOM) protein Fis 1 is thought to be a Dip 1 receptor, this has not been confirmed. To analyze the mechanism of Drp 1 recruitment, we manipulated expression of mitochondria] fission and fusion proteins and demonstrated that (i) mitochondrial fission factor (Mff)-knockdown released the Drp 1 foci from MOM accompanied by network extension, while Mff-overexpression stimulated mitochondrial recruitment of Drpl accompanied by mitochondrial fission ; (ii) Mff-dependent mitochondrial fission proceeded independent of Fisl ; (iii) Mff mutant with plasma membrane-targeted CAAX motif directed Drpl to the target membrane ; (iv) Mff and Drpl physically interacted in vitro and in vivo ; (v) exogenous stimuli-induced mitochondrial fission and apoptosis were compromised by knockdown of Drp1 and Mff, but not Fisl ; and (vi) conditional knockout of Fis l in colon carcinoma cells revealed that it is dispensable for mitochondrial fission. Thus, Mff, but not hFis 1, functions as an essential factor in mitochondrial recruitment of Drp 1.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report

Research Products

(18 results)

All 2011 2010 2009 Other

All Journal Article Presentation Book Remarks

  • [Journal Article] Molecular Mechanism and Physiologic Functions of Mitochondrial Dynamics.2011

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

      J Biochem. Jan 13(149)

      Pages: 241-251

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanisms and physiologic functions of mitochondrial dynamics2011

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

      J Biochem

      Volume: Vol.149 Pages: 241-251

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mff is an essential factor for recruitment of Drpl during mitochondrial fission in mammalian cells.2010

    • Author(s)
      Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S, Youle RJ, Mihara K.
    • Journal Title

      J.Cell.Biol. Dec 13(191)

      Pages: 1141-1158

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells.2010

    • Author(s)
      Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S, Youle RJ, Mihara K
    • Journal Title

      J Cell Biol

      Volume: Vol.191 Pages: 1141-1158

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial fission factor Drpl is essential for embryonic development and synapse formation in mice.2009

    • Author(s)
      Ishihara N, Nomura M, Jofuku A, Kato H, Suzuki SO, Masuda K, Otera H, Nakanishi Y, Nonaka I, Goto YI, Taguchi N, Morinaga H, Maeda M, Takayanagi R, Yokota S, Mihara K.
    • Journal Title

      Nat Cell Biol. Aug 11(8)

      Pages: 958-966

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial fission factor Drpl is essential for embryonic development and synapse formation in mice2009

    • Author(s)
      Ishihara N, Nomura M, Jofuku A, Kato H, Suzuki SO, Masuda K, Otera H, Nakanishi Y, Nonaka I, Goto Y, Taguchi N, Morinaga H, Maeda M, Takayanagi R, Mihara K
    • Journal Title

      Nature Cell Biology 8

      Pages: 958-966

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Discovery of membrane receptor for mitochondrial fission GTPase Drpl.

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

      Small GTPases in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] ミトコンドリア分裂因子Mffのミトコンドリア分裂における役割2010

    • Author(s)
      大寺秀典、三原勝芳
    • Organizer
      日本細胞生物学会
    • Year and Date
      2010-05-21
    • Related Report
      2010 Final Research Report
  • [Presentation] Mitochondrial fission factor Mff recruits Drp1 to the mitochondrial scission site and mediates mitochondrial fission.2010

    • Author(s)
      大寺秀典、三原勝芳
    • Organizer
      日本細胞生物学会
    • Place of Presentation
      大阪
    • Year and Date
      2010-05-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] Physiological significance of mitochondrial fission in apoptosis progression2009

    • Author(s)
      大寺秀典、三原勝芳
    • Organizer
      日本分子生物学会大会
    • Year and Date
      2009-12-11
    • Related Report
      2010 Final Research Report
  • [Presentation] Physiological significance of mitochondrial fission in apoptosis progression2009

    • Author(s)
      大寺秀典、三原勝芳
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜市・パシフィコ横浜
    • Year and Date
      2009-12-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] ミトコンドリア分裂因子Mff~ミトコンドリア分裂/アポトーシスにおける役割2009

    • Author(s)
      大寺秀典、三原勝芳
    • Organizer
      特定領域研究く蛋白質の社会>班会議
    • Year and Date
      2009-11-12
    • Related Report
      2010 Final Research Report
  • [Book] 膜貫通ドメインによる膜タンパク質の選別輸送実験医学 Vbl.28, No.132010

    • Author(s)
      大寺秀典、三原勝芳、瀬戸口喜代子
    • Related Report
      2010 Final Research Report
  • [Book] ミトコンドリア膜構造変化とアポトーシス細胞工学 Vbl.29, No.52010

    • Author(s)
      大寺秀典、岡敏彦
    • Related Report
      2010 Final Research Report
  • [Book] 細胞工学(ミトコンドリア膜構造変化とアポトーシス制御)2010

    • Author(s)
      大寺秀典、岡敏彦
    • Total Pages
      5
    • Publisher
      秀潤社
    • Related Report
      2010 Annual Research Report
  • [Book] 実験医学(膜貫通ドメインによる膜タンパク質の選別輸送)2010

    • Author(s)
      大寺秀典、瀬戸口喜代子、三原勝芳
    • Total Pages
      5
    • Publisher
      羊土社
    • Related Report
      2010 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.med.kyushu-u.ac.jp/seisaseibutu/people/otera.html

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.protein.bio.titech.ac.jp/result.html

    • Related Report
      2010 Annual Research Report

URL: 

Published: 2009-03-31   Modified: 2016-04-21  

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