• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Collapse of mitochondrial quality control mediated by PINK1 and Parkin causes Parkinson disease

Research Project

Project/Area Number 23687018
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Functional biochemistry
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

MATSUDA Noriyuki  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, 副参事研究員 (10332272)

Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥26,650,000 (Direct Cost: ¥20,500,000、Indirect Cost: ¥6,150,000)
Fiscal Year 2013: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2012: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2011: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
KeywordsPINK1 / Parkin / ミトコンドリア / パーキンソン病 / ユビキチン
Research Abstract

1) We screened for novel Parkin substrate(s) and identified mitochondrial hexokinase I (HKI) as a candidate. Following a decrease in membrane potential, Parkin ubiquitylation of HKI leads to its proteasomal degradation. Moreover, most disease-relevant mutations of Parkin hinder this event and endogenous HKI is ubiquitylated upon dissipation of mitochondrial membrane potential in genuine-Parkin expressing cells, suggesting its physiological importance. 2) The mechanism underlying the homeostatic control of PINK1 remains unknown. We revealed that PINK1 is autophosphorylated following a decrease in membrane potential and that most disease-relevant mutations hinder this event. We demonstrated that PINK1 autophosphorylation occurs at Ser228 and Ser402, residues that are structurally clustered together. We propose that autophosphorylation of Ser228 and Ser402 in PINK1 is essential for efficient mitochondrial localization of Parkin.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (23 results)

All 2014 2013 2012 2011 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results) Presentation (11 results) (of which Invited: 8 results) Remarks (4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] The principal PINK1 and Parkin cellular events triggered in response to dissipation of mitochondrial membrane potential also occur in primary neurons2013

    • Author(s)
      Fumika Koyano, Kei Okatsu, Shinsuke Ishigaki, Yusuke Fujioka, Mayumi Kimura, Keiji Tanaka, Noriyuki Matsuda
    • Journal Title

      Genes to Cells

      Volume: 18 Issue: 8 Pages: 672-81

    • DOI

      10.1111/gtc.12066

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Parkin catalyzed ubiquitin-ester transfer is triggered by PINK1-dependent phosphorylation2013

    • Author(s)
      Masahiro Iguchi, Yuki Kujuro, Kei Okatsu, Fumika Koyano, Hidetaka Kosako, Mayumi Kimura, Norihiro Suzuki, Shinichiro Uchiyama, Keiji Tanaka, Noriyuki Matsuda
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 288 Issue: 30 Pages: 22019-32

    • DOI

      10.1074/jbc.m113.467530

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A dimeric PINK1-containing complex on depolarized mitochondria stimulates Parkin recruitment2013

    • Author(s)
      Kei Okatsu, Midori Uno, Fumika Koyano, Etsu Go, Mayumi kimura, Toshihiko Oka, Keiji Tanaka, Noriyuki Matsuda
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 288 Issue: 51 Pages: 36372-84

    • DOI

      10.1074/jbc.m113.509653

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial hexokinase HKI is a novel substrate of the Parkin ubiquitin ligase2012

    • Author(s)
      Okatsu, K., Iemura, S-I., Koyano, F., Go, E., Kimura, M., Natsume, T., Tanaka, K., and Matsuda, N
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 428 (1) Issue: 1 Pages: 197-202

    • DOI

      10.1016/j.bbrc.2012.10.041

    • Related Report
      2013 Final Research Report 2012 Annual Research 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
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 遺伝性パーキンソン病関連分子PINK1は自己リン酸化を介して「ミトコンドリア異常」シグナルをParkinに伝達する細胞工学2012

    • Author(s)
      松田憲之
    • Journal Title

      Hot Press(秀潤社)

      Volume: Vol.31, No.12 Pages: 1374-75

    • Related Report
      2013 Final Research Report
  • [Journal Article] Parkin mediates apparent E2-independent monoubiquitination in vitro and contains an intrinsic activity that catalyzes polyubiquitination2011

    • Author(s)
      Chew, KCM*., Matsuda, M*., Saisho, K., Lim, GGY., Chai, C., Tan, HM., Tanaka, K., Lim, K-L.(*equally contribution)
    • Journal Title

      PloS ONE.

      Volume: 6(5) Issue: 5 Pages: e19720-e19720

    • DOI

      10.1371/journal.pone.0019720

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Identification of the Genuine Substrate of PINK1 that Activates Parkin2014

    • Author(s)
      Noriyuki Matsuda
    • Organizer
      Keystone Symposium, Mitochondrial Dynamics and Physiology (Q5)
    • Place of Presentation
      Santa Fe Community Convention Center, Santa Fe, New Mexico, USA
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 遺伝性パーキンソン病の関連因子 PINK1 と Parkin がミトコンドリア異常をモニターする仕組み2013

    • Author(s)
      松田憲之
    • Organizer
      第86回 日本生化学会大会シンポジウム「ミトコンドリアワールド:エネルギー生産から生体内環境保全まで」
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Parkin catalyzes ubiquitylation on damaged mitochondria via a (ubiquitin-ester)-transfer rather than an E2-recruitment2013

    • Author(s)
      Noriyuki Matsuda and Keiji Tanaka
    • Organizer
      International Symposium on Mitochondria 2013
    • Place of Presentation
      Roppongi Hills
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] PINK1による「ミトコンドリア異常」シグナル:膜電位の低下はPINK1の自己リン酸化を介して伝達されるAutophosphorylation of PINK1 upon the dissipation of mitochondrial membrane potential is essential for recruitment of Parkin to damaged mitochondria2012

    • Author(s)
      松田憲之,尾勝圭,岡敏彦,小迫英尊,田中啓二
    • Organizer
      第35回日本神経科学大会inシンポジウム「神経変性機序解明に向けた新たな展開」
    • Place of Presentation
      名古屋(名古屋国際会議場)
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] 家族性パーキンソン病の責任遺伝子産物 Parkin のE3 酵素活性はミトコンドリアによって制御される2012

    • Author(s)
      松田憲之
    • Organizer
      第85回 日本生化学会大会
    • Place of Presentation
      福岡(福岡国際会議場)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] PINK1 による「ミトコンドリア異常」シグナル:膜電位の低下は PINK1 の自己リン酸化を介して伝達される2012

    • Author(s)
      松田憲之
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋(名古屋国際会議場)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Phosphorylation and activation of PINK1 in response to dissipation of mitochondrial membrae potential recruits cytosolic Parkin to damaged mitochondria for selective clearance2011

    • Author(s)
      松田憲之, 尾勝圭, 岡敏彦, 田中啓二
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2011-12-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] ミトコンドリア異常を伝えるPINK1シグナル2011

    • Author(s)
      松田憲之, 尾勝圭, 田中啓二
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都(国立京都国際会館)(招待講演)
    • Year and Date
      2011-09-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] ミトコンドリアから見た神経変性機序 パーキンソン病を例に2011

    • Author(s)
      松田憲之
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋(名古屋国際会議場)(招待講演)
    • Year and Date
      2011-05-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] 「ストレスシグナル研究の最前線」ミトコンドリア異常を伝えるPINK1シグナル(PINK1 as a signal component of damaged mitochondria)2011

    • Author(s)
      松田憲之,尾勝圭,田中啓二
    • Organizer
      第84回日本生化学会大会シンポジウム2S2a
    • Place of Presentation
      京都(国立京都国際会館)
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Parkin catalyzes ubiquitylation via a (ubiquitin-ester)-transfer rather than an E2-recruitment

    • Author(s)
      Noriyuki Matsuda and Keiji Tanaka
    • Organizer
      4th IGAKUKEN International Symposium on Cutting-edge of the Ubiquitin-Proteasome System
    • Place of Presentation
      公益財団法人東京都医学総合研究所
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Remarks]

    • URL

      http://www.igakuken.or.jp/pro-meta/

    • Related Report
      2013 Final Research Report
  • [Remarks] 蛋白質代謝研究室の HP

    • URL

      http://www.igakuken.or.jp/pro-meta/index.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] パーキンソン病発症を抑える分子メカニズムを解明

    • URL

      http://www.igakuken.or.jp/research/topics/2012/0822.html

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.igakuken.or.jp/pro-meta/

    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] パーキンソン病のバイオマーカーおよびその利用2014

    • Inventor(s)
      松田憲之、小谷野史香、尾勝圭、呉越、木村まゆみ、佐伯泰
    • Industrial Property Rights Holder
      松田憲之、小谷野史香、尾勝圭、呉越、木村まゆみ、佐伯泰
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-02-18
    • Related Report
      2013 Annual Research Report

URL: 

Published: 2011-04-06   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi