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Regulatory mechanisms of cellular circadian clock via mitochondria

Research Project

Project/Area Number 16H04651
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurophysiology / General neuroscience
Research InstitutionUniversity of Toyama

Principal Investigator

IKEDA MASAYUKI  富山大学, 大学本部, 理事・副学長 (10288053)

Co-Investigator(Kenkyū-buntansha) 池田 正明  埼玉医科大学, 医学部, 教授 (80232198)
森岡 絵里  富山大学, 学術研究部理学系, 助教 (80756122)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywords体内時計 / 細胞内カルシウム / 細胞内プロトン / 視交叉上核 / 外側ニューロン / 概日ペースメーカー / 行動リズム / ミトコンドリア / Ca2+濃度 / H+濃度 / 時計遺伝子 / 蛍光ライブセルイメージング / 細胞内H+ / 細胞内Ca2+ / 分子・細胞神経科学
Outline of Final Research Achievements

To anticipate daily energy demands, cellular metabolic pathways are closely associated with circadian clock mechanisms. Molecule to molecule interactions and enzymatic phosphorylation intermediate molecular clock movements and metabolisms whereas related ionic movements were not well characterized. Here we find that mitochondrial cation antiporter (LETM1) drives circadian cytosolic H+ rhythms in Drosophila lateral neurons and cytosolic Ca2+ rhythms in rat suprachiasmatic nucleus neurons. These ionic oscillations may drive neurophysiological output rhythms in circadian pacemaker neurons. Moreover, knockdown of LETM1 prolonged or damped clock gene transcriptional and translational rhythms in circadian pacemaker neurons. Therefore, circadian ionic rhythms caused in parallel with metabolic activities via LETM1 could be a feedback signal to stabilize core clock oscillations, which strengthen neural pacemaker functions.

Academic Significance and Societal Importance of the Research Achievements

体内時計発振は、時計遺伝子産物の相互作用や転写制御により説明されてきた。また近年では、代謝振動が組み合わさってリズムを形成することが明らかにされている。本研究ではミトコンドリア内膜に存在するLETM1を介したCa+/H+の交換に概日リズムが存在することや、これらのイオン濃度リズムが時計遺伝子転写翻訳リズムや行動リズム形成に重要であること(イオンによるフィードバック)を明らかにした。これまで、哺乳類のペースメーカーニューロンでは概日Ca2+濃度リズムが存在することは知られていたが、ハエでは、Ca2+濃度に代わりH+濃度がリズムを刻んでいることを、初めて明らかにした点も大きな学術的な成果といえる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (14 results)

All 2020 2019 2018 2017 2016

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] 時計遺伝子と睡眠覚醒2020

    • Author(s)
      望月貴年、池田真行
    • Journal Title

      睡眠医療

      Volume: 14 Pages: 73-78

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Nighttime activities and peripheral clock oscillations depend on Wolbachia endosymbionts in flies2018

    • Author(s)
      Morioka E, Oida M, Tsuchida T, & Ikeda M
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 15432-15432

    • DOI

      10.1038/s41598-018-33522-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histamine receptor regulates molecular clock oscillations in human retinal pigment epithelial cells via H1 receptors2018

    • Author(s)
      Morioka E, Kanda Y, Koizumi H, Miyamoto T, & Ikeda M
    • Journal Title

      Frontiers in Endocrinology

      Volume: 9 Pages: 108-108

    • DOI

      10.3389/fendo.2018.00108

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of molecular clock oscillations and phagocytic activity via muscarinic Ca2+ signaling in human retinal pigment epithelial cells2017

    • Author(s)
      Ikarashi R, Akechi H, Kanda Y, Ahmad A, Takeuchi K, Morioka E, Sugiyama T, Ebisawa T, Ikeda M & Ikeda M
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 44175-44175

    • DOI

      10.1038/srep44175

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Bimodal modulation of store-operated Ca2+ channels by clozapine in astrocytes2016

    • Author(s)
      Kanda Y, Okada M, Ikarashi R, Morioka E, Kondo T, & Ikeda M
    • Journal Title

      Neuroscience Letters

      Volume: 635 Pages: 56-60

    • DOI

      10.1016/j.neulet.2016.10.027

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Mitochondrial LETM1 drives intracellular proton rhythm in Drosophila pacemaker neurons2019

    • Author(s)
      森岡絵里,Todd C. Holmes,池田真行
    • Organizer
      第26回日本時間生物学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Effects of mitochondrial LETM1 knockdown on cytosolic calcium dynamics2019

    • Author(s)
      小泉隼人,森玉早貴,宮嶋梨沙,村山望,森岡絵里,池田真行
    • Organizer
      第26回日本時間生物学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Histamine H1 receptors regulate sleep and circadian clock oscillations: Implication from model studies using rats and human cell lines2018

    • Author(s)
      51.宮本翼、小泉隼人、纐纈貴大、橋野昇敬、森岡絵里、池田真行
    • Organizer
      The 9th congress of Asian Sleep Research Society (ASRS)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Remaining issues for the circadian control of animal behavior2018

    • Author(s)
      池田真行
    • Organizer
      Oriental International Sleep Medicine Summit Forum
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Clozapine induced cytosolic Ca2+ mobilizations via store-operated Ca2+ channels in astrocytes2017

    • Author(s)
      森岡絵里、神田柚紀、岡田美穂、五十嵐梨菜、池田真行
    • Organizer
      第94回日本生理学会
    • Place of Presentation
      浜松
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] Leptin enhanced cholecystokinin signaling but not vice versa; A model study for satiety signal interactions2017

    • Author(s)
      池田真行、武藤清和、松葉名奈美、モハマドシャヒド、森岡絵里
    • Organizer
      第94回日本生理学会
    • Place of Presentation
      浜松
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] 体内時計ニューロンのリズム発振におけるミトコンドリアLETM1の役割2017

    • Author(s)
      神田柚紀,森玉早貴,森岡絵里,池田真行
    • Organizer
      第24回日本時間生物学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 細胞内共生微生物が宿主の行動リズムに及ぼす影響2017

    • Author(s)
      森岡絵里,土`田努,池田真行
    • Organizer
      第24回日本時間生物学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Sleep-induced circadian phase-shifts revealed by daily ketotifen injections in rats2016

    • Author(s)
      アハマドアルサワフ、橋野昇敬、神田柚紀、森岡絵里、池田真行
    • Organizer
      第23回日本時間生物学会学術大会
    • Place of Presentation
      名古屋
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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