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Elucidation of the mechanism of mitochondrial maintenance by Parkinson's disease gene products

Research Project

Project/Area Number 26461280
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionJuntendo University

Principal Investigator

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

Co-Investigator(Renkei-kenkyūsha) IMAI Yuzuru  順天堂大学, 医学研究科, 先任准教授 (30321730)
INOSHITA Tsuyoshi  順天堂大学, 医学研究科, 助教 (20601206)
Research Collaborator HATTORI Nobutaka  順天堂大学, 医学部, 教授 (80218510)
AKAMATSU Wado  順天堂大学, 医学研究科, 特任教授 (60338184)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsParkin / PINK1 / パーキンソン病 / マイトファジー / mitophagy / 遺伝性パーキンソン病
Outline of Final Research Achievements

The Parkinson’s disease gene products PINK1 and Parkin are involved in the maintenance of mitochondrial functions. It has been demonstrated that PINK1 activates Parkin through its phosphorylation, which leads to selective removal of damaged mitochondria.
This study uncovered that PINK1 and Parkin have a role to amplify the phospho-ubiquitin chains on the damaged mitochondria as their degradation signal. Moreover, the amplification system of the phospho-ubiquitin signal was compromised in dopaminergic neurons derived for patient’s iPS cells, which strongly suggests that the dysfunction of this system is involved in PD pathogenesis.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (11 results)

All 2017 2016 2015 2014

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (6 results) (of which Invited: 1 results) Book (1 results)

  • [Journal Article] Evidence that phosphorylated ubiquitin signaling is involved in the etiology of Parkinson’s disease2017

    • Author(s)
      Shiba-Fukushima Kahori、Ishikawa Kei-Ichi、Inoshita Tsuyoshi、Izawa Nana、Takanashi Masashi、Sato Shigeto、Onodera Osamu、Akamatsu Wado、Okano Hideyuki、Imai Yuzuru、Hattori Nobutaka
    • Journal Title

      Human Molecular Genetics

      Volume: 26 Pages: 3172-3185

    • DOI

      10.1093/hmg/ddx201

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phosphorylation of mitochondrial polyubiquitin by PINK1 promotes Parkin mitochondrial tethering.2014

    • Author(s)
      Shiba-Fukushima K, Arano T, Matsumoto G, Inoshita T, Yoshida S, Ishihama Y, Ryu KY, Nukina N, Hattori N, Imai Y.
    • Journal Title

      PLoS Genet.

      Volume: 10 Issue: 12 Pages: 1004861-1004861

    • DOI

      10.1371/journal.pgen.1004861

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lysine 63-linked polyubiquitination is dispensable for Parkin-mediated mitophagy.2014

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

      J Biol Chem.

      Volume: 289 Issue: 48 Pages: 33131-6

    • DOI

      10.1074/jbc.c114.580944

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [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
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Evidence that phosphorylated ubiquitin signaling is involved in the etiology of Parkinson’s disease.2016

    • Author(s)
      Shiba K, Ishikawa K, Inoshita T, Akamatsu W, Hideyuki O, Imai Y, Hattori N
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] In vivo evidence for the involvement of phospho-ubiquitin signal.2016

    • Author(s)
      Shiba K, Ishikawa K, Takanashi M, Akamatsu W, Imai Y, Hattori N
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      横浜
    • Year and Date
      2016-07-22
    • Related Report
      2016 Research-status Report
  • [Presentation] PINK1-Parkinシグナルによるミトコンドリアの品質管理機構2015

    • Author(s)
      柴 佳保里
    • Organizer
      第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-02
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Phosphorylation of Mitochondrial K63-Linked Polyubiquitin by PINK1 Promotes Parkin Mitochondrial Tethering2015

    • Author(s)
      福嶋 佳保里
    • Organizer
      第56回日本神経学会学術大会
    • Place of Presentation
      新潟コンベンションセンター
    • Year and Date
      2015-05-23
    • Related Report
      2015 Research-status Report
  • [Presentation] Lysine 63-linked polyubiquitination is dispensable for Parkin-mediated mitophagy2014

    • Author(s)
      Shiba-Fukushima K, Inoshita T, Hattori N, Imai Y
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-11
    • Related Report
      2014 Research-status Report
  • [Presentation] PINK1-Parkinミトコンドリア品質管理機構に関与する分子の探索2014

    • Author(s)
      柴 佳保里、井下 強、梅崎 勇次郎、今居 譲、服部 信孝
    • Organizer
      第55回日本神経学会学術大会
    • Place of Presentation
      福岡
    • Year and Date
      2014-05-23
    • Related Report
      2014 Research-status Report
  • [Book] 実験医学2015

    • Author(s)
      今居 譲、柴佳保里、服部信孝
    • Total Pages
      134
    • Publisher
      羊土社
    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2019-03-29  

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