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Identification of molecular mechanism of mitochondrial quality control by PINK1-Parkin pathway

Research Project

Project/Area Number 24790896
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionJuntendo University

Principal Investigator

SHIBA Kahori  順天堂大学, 医学(系)研究科(研究院), 研究員 (30468582)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsParkin / PINK1 / 遺伝性パーキンソン病 / ミトコンドリア / mitophagy / マイトファジー
Research Abstract

Drosophila genetics and cell biological studies have revealed that two Parkinson's disease-associated genes PINK1 and parkin are involved in the mitochondrial maintenance. Parkin is activated and translocated to damaged mitochondria in a PINK1 activity depenednt manner. However, it was unclear how PINK1 recruits Parkin to the damaged mitochondria. In this study found that Parkin is phosphorylated by PINK1 upon reduction of mitochondrial membrane potential, which is required for effective Parkin mitochondrial translocation. Our study also revealed that the biological significance of Parkin phosphorylation using Drosophila expressing wild-type or mutant forms of Parkin (SA, SE). In vivo, we suggested that PINK1 mediated phosphorylation of Parkin boosts its ubiquitin-ligase activity and that constitutive activation of Parkin could damage mitochondria, degrading mitochondrial proteins Mitofusin, Miro and the mitochondrial respiratory complex proteins.

Report

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

    (15 results)

All 2014 2013 2012 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (7 results) Remarks (3 results)

  • [Journal Article] PINK1-mediated phosphorylation of Parkin boosts Parkin activity in Drosophila.2014

    • Author(s)
      Shiba-Fukushima K, Inoshita T, Hattori N, Imai Y.
    • Journal Title

      PLoS Genet.

      Volume: Jun 5;10(6) Issue: 6 Pages: 1004391-1004391

    • DOI

      10.1371/journal.pgen.1004391

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tricornered/NDR kinase signaling mediates PINK1-directed mitochondrial quality control and tissue maintenance2013

    • Author(s)
      Wu Z, Sawada T, Shiba K, Liu S, Kanao T, Takahasi R, Hattori N, Imai Y, Lu B
    • Journal Title

      Genes Dev.

      Volume: 27(2) Pages: 157-62

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tricornered/NDR kinase signaling mediates PINK1-directed mitochondrial quality control and tissue maintenance2013

    • Author(s)
      Wu Z, Sawada T, Shiba K, Liu S, Kanao T, Takahashi R, Hattori N, Imai Y, Lu B. .
    • Journal Title

      Genes Dev.

      Volume: 27 Issue: 2 Pages: 157-62

    • DOI

      10.1101/gad.203406.112

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy2012

    • Author(s)
      Kahori Shiba-Fukushima
    • Journal Title

      Scientific Reports

      Volume: 2 Issue: 1 Pages: 1002-1002

    • DOI

      10.1038/srep01002

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [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
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] PINK1によるParkinリン酸化の生理的意義2013

    • Author(s)
      柴-福嶋佳保里、井下強、吉見建二、服部信孝、今居譲
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-03
    • Related Report
      2013 Final Research Report
  • [Presentation] PINK1依存的なParkinのリン酸化修飾はPINK1/Parkin経路マイトファジーに必要である2013

    • Author(s)
      福嶋佳保里、今居譲、吉田繁治、石濱泰、金尾智子、佐藤栄人、服部信孝
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2013-05-30
    • Related Report
      2013 Final Research Report
  • [Presentation] Parkinノックアウトマウスにおける放出機構の検討2013

    • Author(s)
      江口博人、今泉美佳、塚口ケネス、福嶋佳保里、佐藤栄人、舩山学、斉木臣二、波田野琢、久保紳一郎、今居譲、永松信哉、服部信孝
    • Organizer
      第54回日本神経学会学術大会、ポスター
    • Place of Presentation
      東京
    • Year and Date
      2013-05-30
    • Related Report
      2013 Final Research Report
  • [Presentation] PINK1依存的なParkinのリン酸化修飾はPINK1/Parkin経路マイトファジーに必要である2013

    • Author(s)
      福嶋佳保里、吉田繁治、石濱泰、今居譲、服部信孝
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Annual Research Report
  • [Presentation] PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin : aninitial step of mitophagy2012

    • Author(s)
      Imai Y, Shiba-Fukushima K, Yoshida S, Ishihama Y,Hattori N
    • Organizer
      第35回日本分子生物学会年会ワークショップ「オートファジーによる分解の諸相」
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-11
    • Related Report
      2013 Final Research Report
  • [Presentation] PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin : aninitial step of mitophagy2012

    • Author(s)
      Imai Y, Shiba-Fukushima K, Yoshida S, Ishihama Y,Hattori N
    • Organizer
      第35回日本分子生物学会年会、ポスター
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-11
    • Related Report
      2013 Final Research Report
  • [Presentation] PINK1依存的なParkinのリン酸化修飾は、Parkinのミトコンドリア移行とその後のマイトファジー反応に必要である

    • Author(s)
      今居譲、柴佳保里、吉田繁治、石濱泰、服部信孝
    • Organizer
      日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡
    • Related Report
      2012 Research-status Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.juntendo-neurology.com/n-kenkyu-syoukai.html

    • Related Report
      2013 Final Research Report
  • [Remarks] PINK1によるParkinのリン酸化の発見に関するプレスリリース

    • Related Report
      2013 Final Research Report
  • [Remarks] 「順天堂大学、Parkinリン酸化の阻害が若年性パーキンソン病発症に関与か」日経バイオテクOnline 2012年12月19日掲載 Parkinリン酸化の役割をドーパミン神経において解明したことに関するプレスリリース

    • URL

      http://www.juntendo.ac.jp/graduate/pdf/news10.pdf

    • Related Report
      2013 Final Research Report

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

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