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HADH, involved in mitochondrial fatty acid metabolism, regulates temperature acclimation

Research Project

Project/Area Number 21K15141
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
Research InstitutionOsaka University (2023)
Konan University (2021-2022)

Principal Investigator

Okahata Misaki  大阪大学, 大学院生命機能研究科, 特別研究員(RPD) (20880561)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsC. elegans / 高温馴化 / 線虫 / 高温順化 / hadh / ミトコンドリア / 温度 / 3ヒドロキシアシルCoA脱水素酵素 / ミトコンドリア分子 / 脂肪酸代謝 / 低温耐性
Outline of Research at the Start

温度は地球が誕生して以来、常に存在する環境情報であり、動物は温度変化に適応することで生存してきた。現代社会においても地球温暖化は人類が抱える問題のひとつであり、90年後には温度上昇に適応できずに約100万種の動植物が絶滅の危機に瀕するといわれていることから、生体の温度適応機構の解明は重要なテーマである。本研究では、線虫C. elegansの高い温度への馴化に関わるミトコンドリア分子の解析を進め、その温度順化への役割を明らかにする。また、温度順化時の様々な生理的変化を最新の遺伝子によってコードされるインジケーターを用いて解析する。

Outline of Final Research Achievements

To elucidate the mechanism by which animals acclimate to temperature changes, we analyzed temperature acclimation of C. elegans. We screened for genes whose expression was altered by temperature change with RNA sequencing analysis. We focused on hadh gene, which is upregulated upon temperature increase. HADH is known to be involved in β-oxidation of fatty acid metabolism in mitochondria in humans, but it has not been reported to be involved in temperature response. The hadh mutant showed abnormal temperature acclimation with slower acclimation to 25°C compared to the wild-type animals. To identify tissues in which HADH regulates temperature acclimation, we performed expression analysis and tissue-specific rescue experiments. HADH was expressed in the intestine and some neurons. Abnormal temperature acclimation in hadh mutants was restored by expressing the wild-type hadh gene in neurons, suggesting that hadh regulate temperature acclimation by functioning in neurons.

Academic Significance and Societal Importance of the Research Achievements

温度は常に存在する重要な環境情報であり、動物は温度変化に適応する生体メカニズムを備えている。体温調節機能の異常は熱中症やヒートショックなどを引き起こすことから、温度に馴れる仕組みを明らかにすることにより、温度に関わる疾患の解明につながると考えられる。本研究では、モデル動物である線虫C. elegansを用いた温度応答解析から、ミトコンドリアの脂肪酸代謝に関わるHADHが神経系で温度応答を制御することを明らかにした。HADHが温度応答に関わるという報告は本研究によって初めて明らかになったことから、今後解析を進めることにより、温度応答に関わる新規メカニズムの解明が期待される。

Report

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

    (20 results)

All 2024 2023 2022 2021 Other

All Journal Article (3 results) (of which Peer Reviewed: 2 results,  Open Access: 3 results) Presentation (15 results) (of which Int'l Joint Research: 3 results) Remarks (2 results)

  • [Journal Article] Screening for cold tolerance genes in C. elegans, whose expressions are affected by anticancer drugs camptothecin and leptomycin B2024

    • Author(s)
      Okahata Misaki、Sawada Natsumi、Nakao Kenji、Ohta Akane、Kuhara Atsushi
    • Journal Title

      Scientific Reports

      Volume: 14 Issue: 1 Pages: 1-14

    • DOI

      10.1038/s41598-024-55794-z

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular physiology regulating cold tolerance and acclimation of <i>Caenorhabditis elegans</i>2022

    • Author(s)
      OKAHATA Misaki、MOTOMURA Haruka、OHTA Akane、KUHARA Atsushi
    • Journal Title

      Proceedings of the Japan Academy, Series B

      Volume: 98 Issue: 3 Pages: 126-139

    • DOI

      10.2183/pjab.98.009

    • ISSN
      0386-2208, 1349-2896
    • Year and Date
      2022-03-11
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anticancer drugs affect temperature signaling and epigenetic factors in the cold tolerance of Caenorhabditis elegans2022

    • Author(s)
      Okahata Misaki、Sawada Natsumi、Nakao Kenji、Ohta Akane、Kuhara Atsushi
    • Journal Title

      Research Square

      Volume: ND

    • DOI

      10.21203/rs.3.rs-2261648/v1

    • Related Report
      2022 Research-status Report
    • Open Access
  • [Presentation] Neuronal HACD-1 regulates temperature acclimation of C. elegans2023

    • Author(s)
      Yukina Mori, Misaki Okahata, Akihisa Fukumoto, Yohei Minakuchi, Atsushi Toyoda, Akane Ohta, Atsushi Kuhara
    • Organizer
      分子生物学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Neuronal function of HADH is required for temperature acclimation of C. elegans2023

    • Author(s)
      Yukina Mori, Misaki Okahata, Akihisa Fukumoto, Yohei Minakuchi, Atsushi Toyoda, Akane Ohta, Atsushi Kuhara
    • Organizer
      神経科学学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] HADH regulating temperature acclimation function in mitochondria of neuron of C. elegans  温度馴化を制御する遺伝子HADHは線虫の神経細胞のミトコンドリアで機能する2022

    • Author(s)
      Akihisa Fukumoto, Misaki Okahata, Yohei Minakuchi, Atsushi Toyoda, Akane Ohta, Atsushi Kuhara
    • Organizer
      分子生物学会
    • Related Report
      2022 Research-status Report
  • [Presentation] HADH involved in mitochondrial β-oxidation regulates temperature acclimation in interneurons of C.elegans2022

    • Author(s)
      Akihisa Fukumoto, Misaki Okahata, Yohei Minakuchi, Atsushi Toyoda, Akane Ohta, Atsushi Kuhara
    • Organizer
      第60回生物物理学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Mitochondria metabolism in neuron regulates temperature acclimation in C. elegans2022

    • Author(s)
      Akihisa Fukumoto, Misaki Okahata, Yohei Minakuchi, Atsushi Toyoda, Akane Ohta, Atsushi Kuhara
    • Organizer
      11th International Tunicate Meeting (11ITM)
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] "神経細胞のミトコンドリアのHADHが温度馴化を制御する HADH in mitochondria of neuron regulates temperature acclimation in C. elegans"2022

    • Author(s)
      Akihisa Fukumoto, Misaki Okahata, Yohei Minakuchi, Atsushi Toyoda, Akane Ohta, Atsushi Kuhara
    • Organizer
      Neuro2022
    • Related Report
      2022 Research-status Report
  • [Presentation] HADH functioning in neural cells regulates cold acclimation in C. elegans2021

    • Author(s)
      Akihisa Fukumoto, Misaki Okahata, Yohei Minakuchi, Atsushi Toyoda, Akane Ohta, Atsushi Kuhara
    • Organizer
      比較生理生化学会
    • Related Report
      2021 Research-status Report
  • [Presentation] HADH which functions in neural cells regulates temperature acclimation in C. elegans2021

    • Author(s)
      Akihisa Fukumoto, Misaki Okahata, Yohei Minakuchi, Atsushi Toyoda, Akane Ohta, Atsushi Kuhara
    • Organizer
      日本分子生物学会
    • Related Report
      2021 Research-status Report
  • [Presentation] C. elegans homologue of HADH involved in human mitochondrial fatty acid metabolism regulates neural function in temperature acclimation2021

    • Author(s)
      Akihisa Fukumoto, Misaki Okahata, Yohei Minakuchi, Atsushi Toyoda, Akane Ohta, Atsushi Kuhara
    • Organizer
      生物物理学会
    • Related Report
      2021 Research-status Report
  • [Presentation] HADH in beta oxidation reaction of fatty acid metabolism of mitochondria regulates cold acclimation2021

    • Author(s)
      Akihisa Fukumoto, Misaki Okahata, Yohei Minakuchi, Atsushi Toyoda, Akane Ohta, Atsushi Kuhara
    • Organizer
      遺伝学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 線虫C. elegansの低温馴化は神経系におけるミトコンドリア脂肪酸β-酸化関連分子によって制御される2021

    • Author(s)
      Akihisa Fukumoto, Misaki Okahata, Yohei Minakuchi, Atsushi Toyoda, Akane Ohta, Atsushi Kuhara
    • Organizer
      動物学会
    • Related Report
      2021 Research-status Report
  • [Presentation] HADH involved in beta-oxygen reaction regulates cold acclimation in neurons2021

    • Author(s)
      Akihisa Fukumoto, Misaki Okahata, Yohei Minakuchi, Atsushi Toyoda, Akane Ohta, Atsushi Kuhara
    • Organizer
      線虫研究の未来を創る会
    • Related Report
      2021 Research-status Report
  • [Presentation] Cold acclimation regulated by neural fatty acid metabolism in mitochondria via HADH2021

    • Author(s)
      Akihisa Fukumoto, Misaki Okahata, Yohei Minakuchi, Atsushi Toyoda, Akane Ohta, Atsushi Kuhara
    • Organizer
      第44回日本神経科学大会、第1回 CJK 国際会議(The 6st China-Japan-Korea International Meeting)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] HACD-1 in neural cells regulate cold acclimation in C. elegans2021

    • Author(s)
      Akihisa Fukumoto, Misaki Okahata, Yohei Minakuchi, Atsushi Toyoda, Akane Ohta, Atsushi Kuhara
    • Organizer
      23th C. elegans International conference
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] ミトコンドリアの脂肪酸代謝に関わるHACD-1は神経系において線虫の低温馴化を制御する2021

    • Author(s)
      Akihisa Fukumoto, Misaki Okahata, Yohei Minakuchi, Atsushi Toyoda, Akane Ohta, Atsushi Kuhara
    • Organizer
      動物学会近畿支部会
    • Related Report
      2021 Research-status Report
  • [Remarks] 所属研究室ホームページ

    • URL

      http://kuharan.com

    • Related Report
      2022 Research-status Report
  • [Remarks] 所属研究室ホームページ

    • URL

      http://kuharan.com/index.html

    • Related Report
      2021 Research-status Report

URL: 

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

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