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Reconstitution of Parkin activation and recruitment to target membrane

Research Project

Project/Area Number 18K06237
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

YAMANO Koji  公益財団法人東京都医学総合研究所, 基礎医科学研究分野, 主席研究員 (30547526)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsミトコンドリア / ユビキチン / オートファジー / マイトファジー / Parkin / PINK1 / RBR型E3 / RBRリガーゼ
Outline of Final Research Achievements

Mitochondrial quality control is an essential process to maintain cell homeostasis. Parkin and PINK1, gene products mutated in a genetic Parkinsonism play critical roles in ubiquitination of mitochondrial outer membrane proteins, which leads to elimination of damaged mitochondria via autophagy. In this study, I aimed to identify E2 enzymes for Parkin and reconstitute Parkin activation followed by membrane association. I identified several E2 enzymes that interact with activated Parkin and reconstituted Parkin-mediated ubiquitination reactions using isolated mitochondria. I also applied these methods for the discovery of novel interactions between OPTN, one of the autophagy adaptors, and ATG9A.

Academic Significance and Societal Importance of the Research Achievements

ダメージを受けた不良ミトコンドリアを適切に除去することは細胞の恒常性維持に重要であり、その機能が破綻するとパーキンソン病などの神経変性疾患に陥る。本研究は不良ミトコンドリアを選択的に分解・除去するParkinとPINK1の機能解析に焦点を当てた。そしてParkinの活性化に必要なユビキチン結合酵素を複数同定し、ミトコンドリアのユビキチン化反応を再構成した。また、不良ミトコンドリアがオートファジーによって正しく認識されるための新規な相互作用(OPTN-ATG9A)を見出した。これらの成果は不良ミトコンドリア分解の根本的理解の一助となった。

Report

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

    (11 results)

All 2021 2020 2019 Other

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

  • [Journal Article] Mammalian BCAS3 and C16orf70 associate with the phagophore assembly site in response to selective and non-selective autophagy2021

    • Author(s)
      Kojima W, Yamano K, Kosako H, Imai K, Kikuchi R, Tanaka K, Matsuda N
    • Journal Title

      Autophagy

      Volume: - Issue: 8 Pages: 1-26

    • DOI

      10.1080/15548627.2021.1874133

    • NAID

      120007174412

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular mechanisms and physiological functions of mitophagy2021

    • Author(s)
      Onishi Mashun、Yamano Koji、Sato Miyuki、Matsuda Noriyuki、Okamoto Koji
    • Journal Title

      The EMBO Journal

      Volume: 40 Issue: 3 Pages: 1-1

    • DOI

      10.15252/embj.2020104705

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Critical role of mitochondrial ubiquitination and the OPTN?ATG9A axis in mitophagy2020

    • Author(s)
      Yamano Koji、Kikuchi Reika、Kojima Waka、Hayashida Ryota、Koyano Fumika、Kawawaki Junko、Shoda Takuji、Demizu Yosuke、Naito Mikihiko、Tanaka Keiji、Matsuda Noriyuki
    • Journal Title

      Journal of Cell Biology

      Volume: 219 Issue: 9 Pages: 1-23

    • DOI

      10.1083/jcb.201912144

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Two sides of a coin: Physiological significance and molecular mechanisms for damage-induced mitochondrial localization of PINK1 and Parkin2020

    • Author(s)
      Matsuda Noriyuki、Yamano Koji
    • Journal Title

      Neuroscience Research

      Volume: in press Pages: 16-24

    • DOI

      10.1016/j.neures.2020.03.009

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Two different axes CALCOCO2-RB1CC1 and OPTN-ATG9A initiate PRKN-mediated mitophagy2020

    • Author(s)
      Yamano Koji、Youle Richard J.
    • Journal Title

      Autophagy

      Volume: 16 Issue: 11 Pages: 2105-2107

    • DOI

      10.1080/15548627.2020.1815457

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Parkin‐mediated ubiquitylation redistributes MITOL/March5 from mitochondria to peroxisomes2019

    • Author(s)
      Koyano Fumika、Yamano Koji、Kosako Hidetaka、Kimura Yoko、Kimura Mayumi、Fujiki Yukio、Tanaka Keiji、Matsuda Noriyuki
    • Journal Title

      EMBO reports

      Volume: 20 Issue: 12

    • DOI

      10.15252/embr.201947728

    • NAID

      120006942558

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Parkin recruitment to impaired mitochondria for nonselective ubiquitylation is facilitated by MITOL2019

    • Author(s)
      Koyano Fumika、Yamano Koji、Kosako Hidetaka、Tanaka Keiji、Matsuda Noriyuki
    • Journal Title

      Journal of Biological Chemistry

      Volume: 294 Issue: 26 Pages: 10300-10314

    • DOI

      10.1074/jbc.ra118.006302

    • NAID

      120006959752

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Critical Roles of Ubiquitin and Autophagy Adaptors in Mitochondria-Selective Degradation2020

    • Author(s)
      Koji Yamano
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ストレスに応答した損傷ミトコンドリアの選択的分解2019

    • Author(s)
      山野 晃史
    • Organizer
      第14回日本臨床ストレス応答学会大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Mitochondrial Degradation: Dance with Ubiquitin and Autophagy2019

    • Author(s)
      Koji Yamano
    • Organizer
      AUS-OsakaMito2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] ユビキチンプロジェクトHP

    • URL

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

    • Related Report
      2020 Annual Research Report 2019 Research-status Report 2018 Research-status Report

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

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