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Functional analysis of AIF in the nucleus and mitochondria to understand acute encephalopathy caused by mushroom poisoniing

Research Project

Project/Area Number 15K08062
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Environmental and hygienic pharmacy
Research InstitutionNational Institute of Health Sciences

Principal Investigator

Kondo Kazunari  国立医薬品食品衛生研究所, 生化学部, 部長 (40270623)

Research Collaborator Nakamura Kosuke  
Kato Reiko  
Sakata Kozue  
Project Period (FY) 2015-04-01 – 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsスギヒラタケ / 急性脳症 / アポトーシス誘導因子 / アポトーシス / AIF / 食中毒 / 細胞死 / 担子菌 / 脳症 / きのこ
Outline of Final Research Achievements

To clarify the role of AIF in the nucleus and cytosol, we constructed an AIF mutant, which constantly resides in mitochondria using CRISPR/Cas9. Using the mitochondria resident non-releasable AIF, we examined cell viability, differentiation potential, gene expression profiles. The mutant AIF-carrying cells grew slowly and NGF-derived differentiation was completely blocked. The release of AIF may also be indispensable to cell proliferation and differentiation. DNA microarray analysis revealed that several genes involving in cell proliferation, differentiation, neurite out growth, such as S100 calcium-binding protein A, HSP70, early growth response-1, epidermal growth factor receptor, were significantly down-regulated. To summarize, AIF has a novel function to regulate gene ezpression related to cell proliferation and differentiation. The results also help understand refractory neurological disorders.

Academic Significance and Societal Importance of the Research Achievements

本研究では、食中毒で急性脳症により19名の死者を出したスギヒラタケきのこの原因物質とその作用メカニズム、急性脳症との関りの解明を目指すものである。これまでに、細胞毒性成分として単離した脂肪酸が新規細胞死経路により細胞を死に至らしめることを明らかにし、その制御分子AIFはこれまで知られていない機構で細胞の維持に関わっていること、および関与する遺伝子群を推定した。本研究の成果は、食中毒原因解明だけではなく、AIFにより多様な遺伝子発現調節機構への関与の結果は今後神経難病の原因を考えるうえでも極めて重要な知見となると考えられる。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (4 results)

All 2018 2017

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

  • [Journal Article] Molecular phylogenetic analysis of new Entoloma rhodopolium-related species in Japan and its identification method using PCR-RFLP2017

    • Author(s)
      Kazunari Kondo, Kosuke Nakamura , Takumi Ishigaki , Kozue Sakata , Saemi Obitsu , Akio Noguchi , Nozomi Fukuda , Eiji Nagasawa , Reiko Teshima , Tomoko Nishimaki-Mogam
    • Journal Title

      Scientific Reports

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Apoptosis-inducing factorのL101/103G変異体は細胞増殖と神経突起形成を阻害する2018

    • Author(s)
      加藤怜子、坂田こずえ、近藤一成
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mitochondria-resident non-releasable AIF mutant may regulate gene expressions related to cell differentiation and proliferation.2018

    • Author(s)
      Kazunari KONDO, Reiko KATO, Kozue SAKATA, & Kosuke NAKAMURA
    • Organizer
      米国・欧州EMBO合同分子生物学会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Apoptosis inducing factor (AIF) 核内作用解明のためのミトコンドリア局在性 AIF 変異体細胞の構築2017

    • Author(s)
      近藤一成
    • Organizer
      日本分子生物学会
    • Related Report
      2017 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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