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Functional analysis of the proteases in mitochondrial matrix.

Research Project

Project/Area Number 15H03096
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied health science
Research InstitutionKyushu University

Principal Investigator

Matsushima Yuichi  九州大学, 医学研究院, 助教 (20571342)

Co-Investigator(Kenkyū-buntansha) 内海 健  九州大学, 医学研究院, 准教授 (80253798)
瀬戸山 大樹  九州大学, 大学病院, 助教 (30550850)
Co-Investigator(Renkei-kenkyūsha) GOTO Yu-ichi  国立精神・神経医療研究センター, 神経研究所疾病研究第二部, 部長 (20225668)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Keywordsミトコンドリア / プロテアーゼ / ミトコンドリアDNA / タンパク質分解 / 老化 / ミトコンドリア病
Outline of Final Research Achievements

Dysfunctional protein quality control in mitochondria is emerging as a key pathogenic mechanism for aging and various diseases. Consistent with an important role in maintaining mitochondrial protein quality control, inherited mutations in proteases and chaperons in mitochondria matrix are associated with various diseases Lon, m-AAA and ClpXP are ATP-dependent proteases that contribute to the degradation of all mitochondrial matrix proteins. As well as their proteolytic role for impaired protein, these proteases contribute for highly regulated proteolytic reactions that are important in mitochondrial function. We describe here the functional analysis of the proteases localized in the mitochondrial matrix.

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリアは細胞のエネルギーを作り出す器官であり、ミトコンドリアの機能異常は老化や疾病を引き起こします。ミトコンドリア内部のタンパク質は細胞質から輸送され、最終的には三種類のタンパク質分解酵素によって消化されます、これらの酵素は白血病の治療薬のターゲットとしても注目されています。本研究では三種類のタンパク質分解酵素のうち、LonとClpXPがどのようなタンパク質を分解しているのかについて解析をしました。LonとClpXPでは分解するタンパク質により好みがあることなどが判明しました。このような基礎的な研究の積み重ねが、やがて老化の予防や白血病の治療に役立つと考えられます。

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (15 results)

All 2018 2017 2016 2015

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (8 results)

  • [Journal Article] Drosophila protease ClpXP specifically degrades DmLRPPRC1 controlling mitochondrial mRNA and translation2017

    • Author(s)
      Matsushima Yuichi、Hirofuji Yuta、Aihara Masamune、Yue Song、Uchiumi Takeshi、Kaguni Laurie S.、Kang Dongchon
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 1-14

    • DOI

      10.1038/s41598-017-08088-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] IBA57 mutations abrogate iron-sulfur cluster assembly leading to cavitating leukoencephalopathy2017

    • Author(s)
      Ishiyama Akihiko、Sakai Chika、Matsushima Yuichi、Noguchi Satoru、Mitsuhashi Satomi、Endo Yukari、Hayashi Yukiko K.、Saito Yoshiaki、Nakagawa Eiji、Komaki Hirofumi、Sugai Kenji、Sasaki Masayuki、Sato Noriko、Nonaka Ikuya、Goto Yu-ichi、Nishino Ichizo
    • Journal Title

      Neurology Genetics

      Volume: 3 Issue: 5

    • DOI

      10.1212/nxg.0000000000000184

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cardiomyocyte-specific loss of mitochondrial p32/C1qbp causes cardiomyopathy and activates stress responses2017

    • Author(s)
      Saito Toshiro、Uchiumi Takeshi、Yagi Mikako、Amamoto Rie、Setoyama Daiki、Matsushima Yuichi、Kang Dongchon
    • Journal Title

      Cardiovascular Research

      Volume: 113 Issue: 10 Pages: 1173-1185

    • DOI

      10.1093/cvr/cvx095

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Doxycycline induces apoptosis via ER stress selectively to cells with a cancer stem cell-like properties: importance of stem cell plasticity2017

    • Author(s)
      Matsumoto Takashi、Uchiumi Takeshi、Monji Keisuke、Yagi Mikako、Setoyama Daiki、Amamoto Rie、Matsushima Yuichi、Shiota Masaki、Eto Masatoshi、Kang Dongchon
    • Journal Title

      Oncogenesis

      Volume: 6 Issue: 11 Pages: 1-11

    • DOI

      10.1038/s41389-017-0009-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ミトコンドリアマトリクスに局在するプロテアーゼの多様な機能2017

    • Author(s)
      相原正宗、松島雄一
    • Journal Title

      KAGAKU TO SEIBUTSU

      Volume: 55 Issue: 4 Pages: 227-229

    • DOI

      10.1271/kagakutoseibutsu.55.227

    • NAID

      130006516035

    • ISSN
      0453-073X, 1883-6852
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ミトコンドリアに局在するプロテアーゼの新たな機能2017

    • Author(s)
      相原正宗、松島雄一
    • Journal Title

      医学のあゆみ

      Volume: 260 Pages: 55-60

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Serum depletion induced cancer stem cell-like phenotype due to nitric oxide synthesis in oncogenic HRas transformed cells.2016

    • Author(s)
      Monji, K., Uchiumi, T., Hoshizawa, S., Yagi, M., Matsumoto, T, Y., Setoyama, D., Matsushima, Y., Gotoh, K., Amamoto, R., and Kang, D.
    • Journal Title

      Oncotarget

      Volume: 7 Issue: 46 Pages: 75221-75234

    • DOI

      10.18632/oncotarget.12117

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ClpXPによるミトコンドリアDNA遺伝子発現制御の解析2018

    • Author(s)
      松島雄一
    • Organizer
      日本農芸化学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒトミトコンドリアマトリクスに局在するプロテアーゼLonの特異的基質の探索2017

    • Author(s)
      松島雄一
    • Organizer
      日本分子生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒトミトコンドリアマトリクスに局在するプロテアーゼLonの特異的基質の探索2017

    • Author(s)
      松島雄一
    • Organizer
      日本ミトコンドリア学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ClpXPによるミトコンドリアDNA遺伝子発現制御の解析2016

    • Author(s)
      松島雄一、廣藤雄太、康東天
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] ショウジョウバエミトコンドリアRNA結合タンパク質の機能解析2016

    • Author(s)
      廣藤雄太、松島雄一、康東天
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] ClpXPによるミトコンドリアDNA遺伝子発現制御の解析2016

    • Author(s)
      松島雄一、廣藤雄太、康東天
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒトミトコンドリアマトリクスに局在するプロテアーゼLonの特異的基質の探索2016

    • Author(s)
      松島雄一、高橋和也、瀬戸山大樹、康東天
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒトミトコンドリアマトリクスに局在するプロテアーゼLonの特異的基質の探索2015

    • Author(s)
      高橋和也、松島雄一、瀬戸山大樹、康東天
    • Organizer
      第15回日本ミトコンドリア学会年
    • Place of Presentation
      福井
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2022-11-04  

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