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Elucidation of mechanisms which determine selectivity of mitophagy in kidney tubular cells.

Research Project

Project/Area Number 17K16082
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Kidney internal medicine
Research InstitutionOsaka University

Principal Investigator

Minami Satoshi  大阪大学, 医学部附属病院, 医員 (00791592)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsオートファジー / マイトファジー / 尿細管 / 近位尿細管 / ミトコンドリア / 1型糖尿病 / 虚血再灌流 / 腎臓学
Outline of Final Research Achievements

Autophagy is a self-degradation system in lysosomes. Especially, autophagic elimination of mitochondria, referred to as mitophagy, plays an important role to maintain mitochondrial quality. In this study, we established tissue-specific mitophagy monitoring mice. We also elucidated that autophagy was activated and protected mitochondrial function in kidney tubules under type 1 diabetes, hyperphosphatemia and AKI-CKD transition, whereas autophagy was repressed under type 2 diabetes. Moreover, our study suggested that mitophagy in kidney tubules was dependent at least in part on PINK1/Parkin pathway.

Academic Significance and Societal Importance of the Research Achievements

本研究では組織特異的にマイトファジーをモニタリングするマウスを作成したが、このマウスを使用することで今後腎疾患に限らず様々な疾患においてマイトファジー活性を正確にモニターすることが可能である。更に遺伝学的スクリーニングや化合物ライブラリーを用いたスクリーニングと併用することによりマイトファジー制御分子機構の解明やマイトファジー活性化薬の開発の一助となることが期待される。また本研究では2型糖尿病の腎尿細管ではマイトファジーが抑制されていることが明らかとなり今後2型糖尿病性腎症に対してマイトファジーを活性化する治療法が有用であることが示唆された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (4 results)

All 2019 2018

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

  • [Journal Article] Proximal Tubule Autophagy Differs in Type 1 and 2 Diabetes2019

    • Author(s)
      Sakai S, Yamamoto T, Takabatake Y, Takahashi A, Namba-Hamano T, Minami S, Fujimura R, Yonishi H, Matsuda J, Hesaka A, Matsui I, Matsusaka T, Niimura F, Yanagita M, Isaka Y.
    • Journal Title

      J Am Soc Nephrol

      Volume: 30(6) Issue: 6 Pages: 929-945

    • DOI

      10.1681/asn.2018100983

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Autophagy Protects Kidney Proximal Tubules from Phosphate-Mediated Mitochondrial Dysfunction2018

    • Author(s)
      Ryuta Fujimura, Takeshi Yamamoto, Yoshitsugu Takabatake, Satoshi Minami, Atsushi Takahashi, Tomoko Namba, Jun Matsuda, Shinsuke Sakai, Isao Matsui, Fumio Niimura, Taiji Matsusaka, Yoshitaka Isaka.
    • Organizer
      American Society of Nephrology Kidney Week 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] オートファジーは高リン負荷による腎尿細管ミトコンドリア傷害に対抗する2018

    • Author(s)
      藤村龍太、山本毅士、高畠義嗣、南聡、酒井晋介、高橋篤史、難波倫子、松田潤、松井功、坂口悠介、濱野高行、新村文男、松阪泰二、猪阪義隆
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Autophagy protects kidney proximal tubules from phosphate-mediated mitochondrial dysfunction2018

    • Author(s)
      Fujimura R, Yamamoto T, Takabatake Y, Minami S, Sakai S, Takahashi A, Namba-Hamano T, Matsuda J, Matsui I, Sakaguchi Y, Hamano T, Niimura F, Matsusaka T, Yoshimori T, Isaka Y.
    • Organizer
      ISN Frontiers 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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