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In silico screening of novel stress response factors regulated by mitochondrial inner membrane proteases

Research Project

Project/Area Number 16K21680
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Life / Health / Medical informatics
Biophysics
Research InstitutionNational Institute of Advanced Industrial Science and Technology

Principal Investigator

Imai Kenichiro  国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (80442573)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsミトコンドリア / 内膜プロテアーゼ / PARL / バイオインフォマティクス / ストレス応答 / タンパク質分解 / プロテアーゼ / in silico スクリーニング
Outline of Final Research Achievements

Importance of proteolytic regulations by mitochondrial inner membrane proteases recently is emerged in mitochondrial and cellular stress responses. However, the proteolytic regulations are poorly understood due to limited numbers of substrates. In this study, we focus on mitochondrial rhomboid protease PARL and then developed prediction pipeline for novel PARL substrates combining mitochondrial targeting sequence prediction, transmembrane domain prediction optimized for mitochondrial inner membrane and PARL cleavage site prediction. Using the prediction pipeline, we performed comprehensive search of PARL substrates against Human proteome. Consequently, we found 54 candidates. Interestingly, three recently discovered PARL substrates are included in the candidates. Thus, list of the candidate proteins found in this study is informative for discovery of novel PARL substrates.

Academic Significance and Societal Importance of the Research Achievements

これまで内膜プロテアーゼPARLの基質の網羅的探索は行われていなかったが、本研究により54個のPARL基質候補が得られた。これらの中には、最近明らかになったPARL基質も含まれており、未発見の基質が含まれている可能性が高い。今後、この基質候補の中から実験的に新規基質を同定できれば、PARLによるミトコンドリアや細胞のストレス応答機構などの機能調節機構の解明を促進させることができる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2019 2018 2017 2016

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Porin Associates with Tom22 to Regulate the Mitochondrial Protein Gate Assembly2019

    • Author(s)
      Sakaue Haruka、Shiota Takuya、Ishizaka Naoya、Kawano Shin、Tamura Yasushi、Tan Kher Shing、Imai Kenichiro、Motono Chie、Hirokawa Takatsugu、Taki Kentaro、Miyata Non、Kuge Osamu、Lithgow Trevor、Endo Toshiya
    • Journal Title

      Molecular Cell

      Volume: 73 Issue: 5 Pages: 1044-1055

    • DOI

      10.1016/j.molcel.2019.01.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Origin and Evolutionary Alteration of the Mitochondrial Import System in Eukaryotic Lineages2017

    • Author(s)
      Fukasawa Y, Oda T, Tomii K and Imai K
    • Journal Title

      Mol Biol Evol.

      Volume: 印刷中 Issue: 7 Pages: 1574-1586

    • DOI

      10.1093/molbev/msx096

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Origin and Evolutionary Alteration of the Mitochondrial Import System in Eukaryotic Lineages2018

    • Author(s)
      Fukasawa Y, Oda T, Tomii K and Imai K
    • Organizer
      YoungMito 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ミトコンドリア内膜局在プロテアーゼPARLにより機能調節を受ける新規基質探索と機能解析2017

    • Author(s)
      今井賢一郎、深沢嘉紀、富井健太郎、Paul Horton
    • Organizer
      ConBio2017
    • Related Report
      2017 Research-status Report
  • [Presentation] In silico screening of novel stress response factors regulated by mitochondrial inner membrane proteases2016

    • Author(s)
      Kenichiro Imai, Yoshinori Fukasawa, Kentaro Tomii, Paul Horton
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Year and Date
      2016-11-27
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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