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New perspective on mitochondrial morphology regulation focusing on nucleoid dynamics

Research Project

Project/Area Number 21K06066
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43030:Functional biochemistry-related
Research InstitutionShimane University (2023)
Osaka University (2021-2022)

Principal Investigator

ISHIHARA Takaya  島根大学, 学術研究院医学・看護学系, 准教授 (70611862)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsmtDNA / ミトコンドリア核様体 / ダイナミクス / 膜ダイナミクス / ミトコンドリア / 核様体ダイナミクス / ミトコンドリアダイナミクス / ミトコンドリアDNA
Outline of Research at the Start

細胞内エネルギーの大半を作り出すミトコンドリアは、分裂と融合によりその膜形態をダイナミックに変化させる、細胞のゲノムとは別の“独自のゲノム”であるミトコンドリアDNA(mtDNA)を保持している、など特徴的な性質を持っている。申請者らの研究で、ミトコンドリアの膜とmtDNAは一部で協調してミトコンドリア機能の維持に働いていることがわかってきたが、その分子機構については未だ不明な点が多く残されている。本申請研究ではmtDNAからなる核様体のダイナミクスの理解からミトコンドリアの膜の形態変化、およびそれらが関わる個体の様々な高次機能の制御機構を明らかにすることを目的とする。

Outline of Final Research Achievements

This research focused on the nucleoid structure and mitochondrial membrane dynamics based on our concept that "the distribution and arrangement of the nucleoid, which structure formed by the mitochondrial genome (mtDNA), is linked to the fission control mechanism of the mitochondrial membrane." Therefore, we approached to clarify the mechanism controlling mitochondrial morphology through molecular insights into the aspect of nucleoid structure and its regulations. During this research period, we analyzed ATAD3 as a molecule that controls the trafficking of the nucleoid and were able to realize a new mechanism from the perspective of the nucleoid regarding the control of mitochondrial dynamics and maintenance of its function.

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリアが分裂と融合によってダイナミックに形態を変化させる動的な特性は、酵母から哺乳動物まで種を超えて普遍的な制御機構を持つ。また、近年の研究から、この特性は分化や細胞応答などさまざまな高次の生命機能を維持するのに重要な機能を持つことが明らかになっている。本研究で得られた知見は、核様体の動きを制御する分子を起点とし、ミトコンドリアの形態や活性制御機構を明らかにしたものである。今後は同様のコンセプトによって、広くミトコンドリアの機能を改善させる分子詳細の解明に貢献できるものである。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (19 results)

All 2023 2022 2021 Other

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (6 results) (of which Invited: 5 results) Book (2 results) Remarks (3 results)

  • [Journal Article] Dynamics of mitochondrial nucleoids as a novel regulatory mechanism of the mitochondrial genome2023

    • Author(s)
      石原 孝也、石原 玲子、石原 直忠
    • Journal Title

      生化学

      Volume: 95 Issue: 5 Pages: 650-654

    • DOI

      10.14952/SEIKAGAKU.2023.950650

    • ISSN
      0037-1017
    • Year and Date
      2023-10-25
    • Related Report
      2023 Annual Research Report
  • [Journal Article] Mitochondrial dynamics define muscle fiber type by modulating cellular metabolic pathways2023

    • Author(s)
      Yasuda Tatsuki、Ishihara Takaya、Ichimura Ayaka、Ishihara Naotada
    • Journal Title

      Cell Reports

      Volume: 42 Issue: 5 Pages: 112434-112434

    • DOI

      10.1016/j.celrep.2023.112434

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MELAS-Derived Neurons Functionally Improve by Mitochondrial Transfer from Highly Purified Mesenchymal Stem Cells (REC)2023

    • Author(s)
      Liu Lu、Yang Jiahao、Otani Yoshinori、Shiga Takahiro、Yamaguchi Akihiro、Oda Yasuaki、Hattori Miho、Goto Tsukimi、Ishibashi Shuichi、Kawashima-Sonoyama Yuki、Ishihara Takaya、Matsuzaki Yumi、Akamatsu Wado、Fujitani Masashi、Taketani Takeshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 24 Pages: 17186-17186

    • DOI

      10.3390/ijms242417186

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of imeglimin on mitochondrial function, AMPK activity, and gene expression in hepatocytes2023

    • Author(s)
      Hozumi Kaori、Sugawara Kenji、Ishihara Takaya、Ishihara Naotada、Ogawa Wataru
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 746-746

    • DOI

      10.1038/s41598-023-27689-y

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular mechanism linking metabolism and innate immunity on mitochondria2022

    • Author(s)
      花田 有希、石原 孝也、石原 直忠
    • Journal Title

      生化学

      Volume: 94 Issue: 2 Pages: 230-235

    • DOI

      10.14952/SEIKAGAKU.2022.940230

    • ISSN
      0037-1017
    • Year and Date
      2022-04-25
    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pearson syndrome-like anemia induced by accumulation of mutant mtDNA and anemia with imbalanced white blood cell lineages induced by Drp1 deletion in a murine model2022

    • Author(s)
      Ishikawa Kaori、Honma Yo、Yoshimi Ayami、Katada Shun、Ishihara Takaya、Ishihara Naotada、Nakada Kazuto
    • Journal Title

      Pharmacological Research

      Volume: 185 Pages: 106467-106467

    • DOI

      10.1016/j.phrs.2022.106467

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mitochondrial nucleoid trafficking regulated by the inner-membrane AAA-ATPase ATAD3A modulates respiratory complex formation2022

    • Author(s)
      Ishihara Takaya、Ban-Ishihara Reiko、Ota Azusa、Ishihara Naotada
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 47

    • DOI

      10.1073/pnas.2210730119

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Non-alcoholic fatty liver disease in mice with hepatocyte-specific deletion of mitochondrial fission factor2021

    • Author(s)
      Takeichi Yukina、Miyazawa Takashi、Sakamoto Shohei、Hanada Yuki、Wang Lixiang、Gotoh Kazuhito、Uchida Keiichiro、Katsuhara Shunsuke、Sakamoto Ryuichi、Ishihara Takaya、Masuda Keiji、Ishihara Naotada、Nomura Masatoshi、Ogawa Yoshihiro
    • Journal Title

      Diabetologia

      Volume: 64 Issue: 9 Pages: 2092-2107

    • DOI

      10.1007/s00125-021-05488-2

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Impact of mitochondrial dynamics on functional maturation in cardiomyocytes2022

    • Author(s)
      石原孝也, 石原直忠
    • Organizer
      第100回 日本生理学会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] ミトコンドリア機能を制御する核様体の動的変化メカニズム2022

    • Author(s)
      石原孝也, 石原直忠
    • Organizer
      第95回 日本生化学会大会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] ミトコンドリアDNAの動的制御を司る翻訳後修飾2021

    • Author(s)
      石原孝也, 石原直忠
    • Organizer
      第20回 日本ミトコンドリア学会年会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 核様体の構造変化が及ぼすミトコンドリア機能への影響2021

    • Author(s)
      石原孝也, 石原直忠
    • Organizer
      第44回 分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 組織分化におけるミトコンドリアダイナミクスの重要性2021

    • Author(s)
      石原孝也, 石原直忠
    • Organizer
      生理研研究会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] ミトコンドリアの膜とゲノムの動的特性が制御する細胞内エネルギー代謝2021

    • Author(s)
      石原孝也, 石原直忠
    • Organizer
      第94回 日本内分泌学会学術総会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Book] ミトコンドリアの膜とDNAのダイナミクスとその制御機構 -増刊 ミトコンドリア 疾患治療の新時代2023

    • Author(s)
      市川 葵, 石原孝也, 石原直忠
    • Total Pages
      245
    • Publisher
      羊土社
    • ISBN
      9784758104098
    • Related Report
      2022 Research-status Report
  • [Book] ミトコンドリアダイナミクス2021

    • Author(s)
      石原直忠ほか82名
    • Total Pages
      458
    • Publisher
      エヌ・ティー・エス
    • ISBN
      9784860437466
    • Related Report
      2021 Research-status Report
  • [Remarks] ミトコンドリアDNAの“動き”の制御で ミトコンドリアの機能を向上

    • URL

      https://resou.osaka-u.ac.jp/ja/research/2022/20221116_1

    • Related Report
      2022 Research-status Report
  • [Remarks] New insights into mitochondrial nucleoid dynamics

    • URL

      https://www.eurekalert.org/news-releases/971640

    • Related Report
      2022 Research-status Report
  • [Remarks] New insights into mitochondrial nucleoid dynamics

    • URL

      https://www.asiaresearchnews.com/content/new-insights-mitochondrial-nucleoid-dynamics

    • Related Report
      2022 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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