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Phosphorylated ubiquitin is critical for mitochondrial quality assurance to inhibit onset of Parkinson's disease.

Research Project

Project/Area Number 15K19037
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

KOYANO Fumika  公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主任研究員 (50747681)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsミトコンドリア / リン酸化ユビキチン / パーキンソン病 / マイトファジー / Parkin / 蛋白質分解 / リン酸化 / ユビキチン
Outline of Final Research Achievements

(1) We have examined phosphorylated ubiquitin staining using sporadic autopsy Parkinson’s disease (PD) patients’ brains to assess the possibility of phosphorylated ubiquitin as a biomarker. If mitochondrial quality was low in sporadic PD patients’ brains, phosphorylated ubiquitin would accumulate at mitochondria. Small amount of phosphorylated ubiquitin signal was detected in healthy midbrain with increasing age. However, in PD midbrain, several types of phosphorylated ubiquitin signals were observed in a broad area and the amount of signal was larger than that of healthy control. This strategy may be a useful diagnostic approach for impaired mitochondria-derived phosphorylated ubiquitin accumulation.
(2) POLGA-mutated PARKIN knockout mice are subjected to behavioral and pathological analysis to assess PD-like phenotype. We are now evaluating whether each mouse group shows decline in motor coordination function and the number of dopaminergic neuron with age.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (12 results)

All 2017 2016 2015 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Remarks (2 results)

  • [Journal Article] Phosphorylated ubiquitin chain is the genuine Parkin receptor.2015

    • Author(s)
      K. Okatsu, F. Koyano, M. Kimura, H. Kosako, Y. Saeki, K. Tanaka and N. Matsuda
    • Journal Title

      The Journal of Cell Biology

      Volume: 209 Issue: 1 Pages: 111-128

    • DOI

      10.1083/jcb.201410050

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Site-specific Interaction Mapping of Phosphorylated Ubiquitin to Uncover Parkin Activation.2015

    • Author(s)
      Koji Yamano, Bruno B. Queliconi, Fumika Koyano, Yasushi Saeki, Takatsugu Hirokawa, Keiji Tanaka§,and Noriyuki Matsuda
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 290 Issue: 42 Pages: 25199-25211

    • DOI

      10.1074/jbc.m115.671446

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Molecular mechanisms underlying PINK1 and Parkin catalyzed ubiquitylation of substrates on damaged mitochondria2015

    • Author(s)
      Fumika Koyano; Noriyuki Matsuda
    • Journal Title

      BBA - Molecular Cell Research

      Volume: 1853 Issue: 10 Pages: 2791-2796

    • DOI

      10.1016/j.bbamcr.2015.02.009

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Parkin機能喪失に由来するパーキンソン病モデルマウスの作製と解析2017

    • Author(s)
      平石萌、小谷野史香、久永眞市、中田和人、田中啓二、松田憲之
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 未定2016

    • Author(s)
      Fumika Koyano
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-12-01
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] A screening mechanism for high-quality mitochondria by phosphorylated ubiquitin2016

    • Author(s)
      Fumika Koyano
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Year and Date
      2016-09-26
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] ミトコンドリア品質管理不全から読み解く遺伝性パーキンソニズム発症の分子機構2016

    • Author(s)
      小谷野史香
    • Organizer
      パーキンソン病と神経科学研究会
    • Place of Presentation
      京都ホテルオークラ(京都府・京都市)
    • Year and Date
      2016-07-16
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Familial Parkinson’s disease and Mitochondrial quality control2016

    • Author(s)
      Fumika Koyano
    • Organizer
      第2回4大学1研合同研究会
    • Place of Presentation
      ホテル京都エミナース(京都府・京都市)
    • Year and Date
      2016-01-11
    • Related Report
      2015 Research-status Report
  • [Presentation] PINK1 PHOSPHORYLATED UBIQUITIN IS A PARKIN ACTIVATOR2015

    • Author(s)
      Fumika Koyano
    • Organizer
      ISN-APSN-ANS 2015 Meeting
    • Place of Presentation
      ケアンズ(オーストラリア)
    • Year and Date
      2015-08-24
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] PINK1によってリン酸化されたユビキチンがParkinの活性を制御する2015

    • Author(s)
      小谷野史香
    • Organizer
      YoungMito2015
    • Place of Presentation
      ホテル一宮シーサイドオーツカ(千葉・一宮町)
    • Year and Date
      2015-07-09
    • Related Report
      2015 Research-status Report
  • [Remarks] ユビキチンプロジェクトの小谷野 史香 研究員が第4回「明日の象徴」研究者部門を受賞しました。

    • URL

      http://www.igakuken.or.jp/protein/

    • Related Report
      2017 Annual Research Report
  • [Remarks] ユビキチンプロジェクトの小谷野 史香 研究員が第4回「明日の象徴」研究者部門を受賞

    • URL

      http://www.igakuken.or.jp/topics/2015/1110.html

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2021-01-27  

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