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Involvement of a new mitochondrial protein in the central nervous system of familial and sporadic Parkinson's disease.

Research Project

Project/Area Number 23791010
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionDepartment of Clinical Research, National Hospital Organization Tokushima National Hospital

Principal Investigator

MAKI Yukiko (KUROTA Yukiko)  独立行政法人国立病院機構徳島病院(臨床研究部), 研究員 (70398014)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords神経分子病態学 / パーキンソン病 / ミトコンドリア / Klokin 1
Research Abstract

Parkin is a neuroprotective protein with many functions, including maintaining mitochondrial homeostasis. Recent evidence suggests that Parkin is recruited from the cytoplasm to damaged mitochondria with low membrane potential. We found that intracellular localization of Parkin changed with cellular growth phase. Parkin was preferentially localized in the mitochondria of cultured cells in the late log phase of growth. The mitochondria with large amounts of Parkin showed preserved membrane potentials even during treatment with carbonyl cyanide m-chlorophenylhydrazone. Here we report a novel protein named Klokin 1 that transports Parkin to the mitochondria. Klokin 1 was localized to the mitochondria and enhanced mitochondrial expression of Parkin. Klokin 1 enhanced cell viability in Parkin-silenced cells. Klokin 1 expression was enhanced in the brains of Parkin-deficient mice but not in an autopsied PARK2 brain. Our findings indicate that mitochondrial Parkin prevents mitochondrial depolarization and cellular apoptosis and that Klokin 1 may compensate for Parkin deficiency.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (11 results)

All 2012 2011 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (4 results) Remarks (1 results)

  • [Journal Article] Parkin interacts with Klokin1 for mitochondrial import and maintenance of membrane potential.2012

    • Author(s)
      Kuroda Y, Sako W, Goto S, Sawada T, Uchida D, Izumi Y, Takahashi T, Kagawa N, Matsumoto M, Matsumoto M, Takahashi R, Kaji R, Mitsui T.
    • Journal Title

      Hum Mol Genet.

      Volume: 21(5) Pages: 991-1003

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Parkin interacts with Klokinl for mitochondrial import and maintenance of membrane potential2012

    • Author(s)
      Kuroda Y
    • Journal Title

      Human Molecular Genetics

      Volume: Vol.21 Issue: 5 Pages: 991-1003

    • DOI

      10.1093/hmg/ddr530

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect on mitochondrial gene of Parkin.2011

    • Author(s)
      Kuroda Y, Fujimoto M, Kaji R, Mitsui T.
    • Journal Title

      J Tokushima Natl Hosp

      Volume: 2 Pages: 32-35

    • NAID

      40019066369

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Examination of cell viability using the primary culture system of skin fibroblast.2011

    • Author(s)
      Fujimoto M, Kuroda Y, Kawamura K, Kaji R, Mitsui T.
    • Journal Title

      J Tokushima Natl Hosp

      Volume: 2 Pages: 23-26

    • NAID

      40019066348

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The effects of FK506 on refractory inflammatory myopathies2011

    • Author(s)
      Mitsui T, Kuroda Y, Ueno S, Kaji R.
    • Journal Title

      Acta Neurol Belg.

      Volume: 111 Pages: 188-194

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] FK506 attenuates thymic output in patients with myasthenia gravis

    • Author(s)
      Mitsui T, Kuroda Y, Ueno S, Matsui N, Kaji R.
    • Journal Title

      Arch Med Sci

      Volume: (in press)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] パーキンのミトコンドリア膜電位に対する関連蛋白の関与2012

    • Author(s)
      牧(黒田) 由紀子
    • Organizer
      53回日本神経学会総会
    • Place of Presentation
      日本・東京
    • Year and Date
      2012-02-21
    • Related Report
      2012 Final Research Report
  • [Presentation] パ-キンのミトコンドリア膜電位に対する関連蛋白の関与2012

    • Author(s)
      牧(黒田)由紀子
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2012 Annual Research Report
  • [Presentation] パーキンの細胞内局在・機能に対する関連蛋白の関与2011

    • Author(s)
      牧(黒田) 由紀子
    • Organizer
      第52回日本神経学会総会
    • Place of Presentation
      日本・名古屋
    • Year and Date
      2011-05-19
    • Related Report
      2012 Final Research Report
  • [Presentation] パーキンの細胞内局在・機能に対する関連蛋白の関与

    • Author(s)
      牧(黒田)由紀子
    • Organizer
      日本神経学会学術大会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://www.tokusimahosp-nho.jp/

    • Related Report
      2012 Final Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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