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Mechanism of mitochondrial fission: from the initial formation of fission sites to the membrane scission

Research Project

Project/Area Number 23770231
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cell biology
Research InstitutionKyushu University

Principal Investigator

OTERA Hidenori  九州大学, 医学研究院, 助教 (40380612)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords生体膜 / ミトコンドリア / 膜形態 / 分裂 / ミトコンドリアダイナミクス / アポトーシス / タンパク質選別輸送 / ペルオキシソーム
Research Abstract

Mitochondrial fission is important for maintaining cellular function, and its dysfunction causes aging, neuronal synaptic loss, and cell death in several human neurologic diseases. The major player of mitochondrial fission is a largely cytosolic member of the dynamin family of GTPases Drp1 in mammals. Endogenous Drp1, observed as dotted structures on mitochondria, was clearly decreased and was dispersed in the cytoplasm in Mff RNAi cells concomitant with mitochondrial network extension. In contrast, Mff overexpression induced mitochondrial fragmentation, concomitant with increased Drp1 recruitment to the mitochondria. These observations indicate that Mff functions as a Drp1 receptor to mediate mitochondrial fission. Drp1 might self-assemble via its ability to homo-oligomerize at Mff-containing foci on the mitochondrial surface, forming spiral structures around the mitochondrial tubules. MiD51/MIEF1 interacts with recombinant Drp1 to inhibit its GTPase activity accompanied by Drp1 oligomerization. In contrast, Mff competes with MiD51/MIEF1 to stimulate Drp1 GTPase activity. Taken together, MiD51/MIEF1 seems to bind oligomerized Drp1 and stabilize them at the surface of the mitochondrial membrane in the GTP-locked state to inhibit mitochondrial fission.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (10 results)

All 2013 2012 2011 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results) Presentation (2 results) Remarks (1 results)

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

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

      Biochim Biophys Acta

      Volume: 1833 Issue: 5 Pages: 1256-1268

    • DOI

      10.1016/j.bbamcr.2013.02.002

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation and physiologic function of GTPases in mitochondrial fusion and fission in mammals.2012

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

      Antioxid Redox Signaling. 2012 Oct 1.

    • URL

      http://online.liebertpub.com/doi/abs/10.1089/ars.2012.4830

    • Related Report
      2012 Final Research Report
  • [Journal Article] Pex5p imports folded tetrameric catalase into peroxisomes by interaction with Pex13p2012

    • Author(s)
      Otera H, Fujiki Y
    • Journal Title

      Traffic

      Volume: 10 Issue: 10 Pages: 1364-1377

    • DOI

      10.1111/j.1600-0854.2012.01391.x

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [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
      2012 Annual Research Report 2012 Final Research Report 2011 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 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Discovery of membrane receptor for mitochondrial fission GTPase Drp12011

    • Author(s)
      Otera Hidenori, Mihara Katsuyoshi
    • Journal Title

      Small GTPases

      Volume: 3 Issue: 3 Pages: 167-172

    • DOI

      10.4161/sgtp.2.3.16486

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] ミトコンドリアの分裂を司る分子とその機能2011

    • Author(s)
      大寺秀典、三原勝芳
    • Organizer
      日本生化学会大会 シンポジウム
    • Place of Presentation
      京都
    • Related Report
      2012 Final Research Report
  • [Presentation] ミトコンドリアの分裂を司る分子とその機能

    • Author(s)
      大寺秀典、三原勝芳
    • Organizer
      84回日本生化学大会(招待講演)
    • Place of Presentation
      京都
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

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

    • Related Report
      2012 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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