• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Study of mitochondrial transporters branched-chain amino acids using genetically encoded fluorescent biosensors

Research Project

Project/Area Number 17H03654
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionKyoto University

Principal Investigator

Imamura Hiromi  京都大学, 生命科学研究科, 准教授 (20422545)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords分岐鎖アミノ酸 / BCAA / イメージング / FRET / 蛍光 / トランスポーター / siRNA / 蛍光バイオセンサー / SLC25A44 / ミトコンドリア / ライブイメージング / バイオセンサー
Outline of Final Research Achievements

Branched-chain amino acids, also known as BCAAs, are important nutrients involved in a variety of physiological functions and diseases. The branched-chain amino acids incorporated into the cell are transported into the mitochondria for metabolism, but the mechanism by which they are transported into the mitochondria has been unclear. We have developed a new fluorescent biosensor, OLIVe, for imaging branched-chain amino acid concentrations in the cytosol and mitochondria, allowing us to examine spatiotemporal dynamics of the amino acids inside a single living cell. This technique was used to screen mitochondrial branched-chain amino acid transporters, and three candidate genes were identified.

Academic Significance and Societal Importance of the Research Achievements

本研究において我々が開発した蛍光バイオセンサーは、オートファジー研究を始め分岐鎖アミノ酸が関与する幅広い生物学領域において重要な研究ツールとなることが期待されます。分岐鎖アミノ酸は様々な生理機能や疾病に関与することから、分岐鎖アミノ酸の生体内動態の理解の増進は、将来的には病気の理解や健康に大きく寄与する可能性が高いと考えられます。

Report

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

    (38 results)

All 2020 2019 2018 2017

All Journal Article (23 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 23 results,  Open Access: 16 results) Presentation (15 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results)

  • [Journal Article] In vivo real‐time ATP imaging in zebrafish hearts reveals G0s2 induces ischemic tolerance2020

    • Author(s)
      Kioka Hidetaka、Kato Hisakazu、Fujita Takeshi、Asano Yoshihiro、Shintani Yasunori、Yamazaki Satoru、Tsukamoto Osamu、Imamura Hiromi、Kogo Mikihiko、Kitakaze Masafumi、Sakata Yasushi、Takashima Seiji
    • Journal Title

      The FASEB Journal

      Volume: 34 Issue: 2 Pages: 2041-2054

    • DOI

      10.1096/fj.201901686r

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Measurement of ATP concentrations in mitochondria of living cells using luminescence and fluorescence approaches2020

    • Author(s)
      Morciano Giampaolo、Imamura Hiromi、Patergnani Simone、Pedriali Gaia、Giorgi Carlotta、Pinton Paolo
    • Journal Title

      Methods in Cell Biology

      Volume: 155 Pages: 199-219

    • DOI

      10.1016/bs.mcb.2019.10.007

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A molecular triage process mediated by RING finger protein 126 and BCL2-associated athanogene 6 regulates degradation of G0/G1 switch gene 22019

    • Author(s)
      Kamikubo Kenta、Kato Hisakazu、Kioka Hidetaka、Yamazaki Satoru、Tsukamoto Osamu、Nishida Yuya、Asano Yoshihiro、Imamura Hiromi、Kawahara Hiroyuki、Shintani Yasunori、Takashima Seiji
    • Journal Title

      Journal of Biological Chemistry

      Volume: 294 Issue: 40 Pages: 14562-14573

    • DOI

      10.1074/jbc.ra119.008544

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NAD+ consumption by PARP1 in response to DNA damage triggers metabolic shift critical for damaged cell survival2019

    • Author(s)
      Murata Michael M.、Kong Xiangduo、Moncada Emmanuel、Chen Yumay、Imamura Hiromi、Wang Ping、Berns Michael W.、Yokomori Kyoko、Digman Michelle A.
    • Journal Title

      Molecular Biology of the Cell

      Volume: 30 Issue: 20 Pages: 2584-2597

    • DOI

      10.1091/mbc.e18-10-0650

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] OLIVe: A Genetically Encoded Fluorescent Biosensor for Quantitative Imaging of Branched-Chain Amino Acid Levels inside Single Living Cells2019

    • Author(s)
      Yoshida Tomoki、Nakajima Hitomi、Takahashi Sena、Kakizuka Akira、Imamura Hiromi
    • Journal Title

      ACS Sensors

      Volume: 4 Issue: 12 Pages: 3333-3342

    • DOI

      10.1021/acssensors.9b02067

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Higd1a improves respiratory function in the models of mitochondrial disorder2019

    • Author(s)
      Nagao Takemasa、Shintani Yasunori、Hayashi Takaharu、Kioka Hidetaka、Kato Hisakazu、Nishida Yuya、Yamazaki Satoru、Tsukamoto Osamu、Yashirogi Shohei、Yazawa Issei、Asano Yoshihiro、Shinzawa‐Itoh Kyoko、Imamura Hiromi、Suzuki Takeo、Suzuki Tsutomu、Goto Yu‐ichi、Takashima Seiji
    • Journal Title

      The FASEB Journal

      Volume: 34 Issue: 1 Pages: 1859-1871

    • DOI

      10.1096/fj.201800389r

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spindle pole body movement is affected by glucose and ammonium chloride in fission yeast2019

    • Author(s)
      Ito H, Sugawara T, Shinkai S, Mizukawa S, Kondo A, Senda H, Sawai K, Ito K, Suzuki S, Takaine M, Yoshida S, Imamura H, Kitamura K, Namba T, Tate SI, Ueno M
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 511 Issue: 4 Pages: 820-825

    • DOI

      10.1016/j.bbrc.2019.02.128

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reliable imaging of ATP in living budding and fission yeast2019

    • Author(s)
      Takaine M, Ueno M, Kitamura K, Imamura H, Yoshida S.
    • Journal Title

      J Cell Sci.

      Volume: 132 Issue: 8 Pages: 1-11

    • DOI

      10.1242/jcs.230649

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PPARα-Mediated Positive-Feedback Loop Contributes to Cold Exposure Memory2019

    • Author(s)
      Alfaqaan Soaad、Yoshida Tomoki、Imamura Hiromi、Tsukano Chihiro、Takemoto Yoshiji、Kakizuka Akira
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 4538-4538

    • DOI

      10.1038/s41598-019-40633-3

    • NAID

      120006591437

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Automatic Quantitative Segmentation of Myotubes Reveals Single-cell Dynamics of S6 Kinase Activation2018

    • Author(s)
      Inoue Haruki、Kunida Katsuyuki、Matsuda Naoki、Hoshino Daisuke、Wada Takumi、Imamura Hiromi、Noji Hiroyuki、Kuroda Shinya
    • Journal Title

      Cell Structure and Function

      Volume: 43 Issue: 2 Pages: 153-169

    • DOI

      10.1247/csf.18012

    • NAID

      130007472951

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Shear stress augments mitochondrial ATP generation that triggers ATP release and Ca2+ signaling in vascular endothelial cells2018

    • Author(s)
      Yamamoto Kimiko、Imamura Hiromi、Ando Joji
    • Journal Title

      American Journal of Physiology-Heart and Circulatory Physiology

      Volume: 315 Issue: 5 Pages: H1477-H1485

    • DOI

      10.1152/ajpheart.00204.2018

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Trace Amount of Galactose, a Major Component of Milk Sugar, Allows Maturation of Glycoproteins during Sugar Starvation2018

    • Author(s)
      Sasaoka Norio、Imamura Hiromi、Kakizuka Akira
    • Journal Title

      iScience

      Volume: 10 Pages: 211-221

    • DOI

      10.1016/j.isci.2018.11.035

    • NAID

      120006715477

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] General anesthetics cause mitochondrial dysfunction and reduction of intracellular ATP levels.2018

    • Author(s)
      Kishikawa JI, Inoue Y, Fujikawa M, Nishimura K, Nakanishi A, Tanabe T, Imamura H, Yokoyama K.
    • Journal Title

      PLoS ONE

      Volume: 13 Issue: 1 Pages: e0190213-e0190213

    • DOI

      10.1371/journal.pone.0190213

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of mitochondrial function in human induced pluripotent stem cells from patients with mitochondrial diabetes due to the A3243G mutation.2018

    • Author(s)
      Matsubara M, Kanda H, Imamura H, Inoue M, Noguchi M, Hosoda K, Kakizuka A, Nakao K.
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 949-949

    • DOI

      10.1038/s41598-018-19264-7

    • NAID

      120006502575

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenitors2018

    • Author(s)
      Oshima Koichi、Watanabe Akira、Nakahata Tatsutoshi、Saito Megumu K. et al.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 497 Issue: 2 Pages: 719-725

    • DOI

      10.1016/j.bbrc.2018.02.139

    • NAID

      120006466601

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Transient Rise in Free Mg 2+ Ions Released from ATP-Mg Hydrolysis Contributes to Mitotic Chromosome Condensation2018

    • Author(s)
      Maeshima Kazuhiro、Matsuda Tomoki、Shindo Yutaka、Imamura Hiromi、Tamura Sachiko、Imai Ryosuke、Kawakami Syoji、Nagashima Ryosuke、Soga Tomoyoshi、Noji Hiroyuki、Oka Kotaro、Nagai Takeharu
    • Journal Title

      Current Biology

      Volume: 28 Issue: 3 Pages: 444-451

    • DOI

      10.1016/j.cub.2017.12.035

    • NAID

      120006380520

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Visualization of long-term Mg2+ dynamics in apoptotic cells using a novel targetable fluorescent probe2017

    • Author(s)
      Matsui Y, Funato Y, Imamura H, Miki H, Mizukami S, Kikuchi K
    • Journal Title

      Chem Sci.

      Volume: 8 Issue: 12 Pages: 8255-8264

    • DOI

      10.1039/c7sc03954a

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Monitoring ATP dynamics in electrically active white matter tracts.2017

    • Author(s)
      Trevisiol A, Saab AS, Winkler U, Marx G, Imamura H, Moebius W, Kusch K, Nave KA, Hirrlinger J.
    • Journal Title

      eLife

      Volume: 6

    • DOI

      10.7554/elife.24241

    • NAID

      120006318886

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct intracellular Ca2+ dynamics regulate apical constriction and differentially contribute to neural tube closure.2017

    • Author(s)
      Suzuki, M., Sato, M., Koyama, H., Hara, Y., Hayashi, K., Yasue, N., Imamura, H., Fujimori, T., Nagai, T., Campbell, RE., Ueno, N.
    • Journal Title

      Development.

      Volume: 144 Issue: 7 Pages: 1307-1316

    • DOI

      10.1242/dev.141952

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes.2017

    • Author(s)
      Shunsuke Kon, et al.
    • Journal Title

      Nature Cell Biology

      Volume: 印刷中 Issue: 5 Pages: 530-541

    • DOI

      10.1038/ncb3509

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] RLR-mediated antiviral innate immunity requires oxidative phosphorylation activity2017

    • Author(s)
      Yoshizumi T, Imamura H, Taku T, Kuroki T, Kawaguchi A, Ishikawa K, Nakada K, Koshiba T
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 5379-5379

    • DOI

      10.1038/s41598-017-05808-w

    • NAID

      120007128833

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ATP Maintenance via Two Types of ATP Regulators Mitigates Pathological Phenotypes in Mouse Models of Parkinson's Disease2017

    • Author(s)
      Nakano Masaki、Imamura Hiromi、Sasaoka Norio、Yamamoto Masamichi、Uemura Norihito、Shudo Toshiyuki、Fuchigami Tomohiro、Takahashi Ryosuke、Kakizuka Akira
    • Journal Title

      EBioMedicine

      Volume: 22 Pages: 225-241

    • DOI

      10.1016/j.ebiom.2017.07.024

    • NAID

      120006338063

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fusion protein analysis reveals the precise regulation between Hsp70 and Hsp100 during protein disaggregation.2017

    • Author(s)
      Hayashi S, Nakazaki Y, Kagii K, Imamura H, Watanabe YH.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 8648-8648

    • DOI

      10.1038/s41598-017-08917-8

    • NAID

      120006364083

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Genetically encoded fluorescent biosensors for understanding of metabolism at single cell level2020

    • Author(s)
      Hiromi Imamura
    • Organizer
      2nd WPI-NanoLSI Special Seminar
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 蛍光バイオセンサーによる生細胞内代謝物イメージング2019

    • Author(s)
      今村博臣
    • Organizer
      日本分析化学会第68年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Genetically encoded fluorescent biosensor for branched-chain amino acids2019

    • Author(s)
      Hiromi Imamura, Tomoki Yoshida, Hitomi Nakajima, Sena Takahashi, Akira Kakizuka
    • Organizer
      第57回日本生物物理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 蛍光バイオセンサーで解き明かす細胞内代謝2019

    • Author(s)
      今村博臣
    • Organizer
      第71回日本生物工学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 蛍光変化のダイナミックレンジを増大させたFRET型バイオセンサーの開発2019

    • Author(s)
      米満茜、垣塚彰、今村博臣
    • Organizer
      日本生体エネルギー研究会第45回討論会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Imaging of metabolites inside living cells2019

    • Author(s)
      Hiromi Imamura
    • Organizer
      Academia Sinica - Kyoto University Bilateral Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 新規発光型ATPバイオセンサーを用いた細胞内および細胞外ATPダイナミクスの定量的観測系の構築2018

    • Author(s)
      松岡篤志、吉田有希、垣塚彰、今村博臣
    • Organizer
      日本生体エネルギー研究会 第44回討論会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Single-cell imaging of intracellular ATP dynamics during apoptosis using a caspase-resistant FRET-based biosensor2018

    • Author(s)
      Imamura H, Sakamoto S, Yoshida T, Kakizuka A
    • Organizer
      International Meeting on Optical Biosensors
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Imaging of intracellular ATP level revealed pannexin1-mediated programmed ATP decrease in apoptosis2017

    • Author(s)
      Imamura Hiromi, Sakamoto Shuichiro, Yoshida Tomoki, Kakizuka Akira
    • Organizer
      19th International Union for Pure and Applied Biophysics Congress / 11th European Biophysics Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] FRET型ATPセンサーを用いたショウジョウバエ神経細胞におけるATPの濃度と消費速度の可視化2017

    • Author(s)
      津山泰一、坪内朝子、碓井理夫、今村博臣、上村匡
    • Organizer
      日本生体エネルギー研究会 第43回討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ルシフェラーゼ断片の相補的再構成を用いた新規発光ATPバイオセンサーの開発2017

    • Author(s)
      松岡篤志、垣塚彰、今村博臣
    • Organizer
      日本生体エネルギー研究会 第43回討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ツメガエル卵細胞におけるATPの役割の検証2017

    • Author(s)
      井尻貴之、岸川淳一、今村博臣、上野秀一、岩尾康宏、横山謙、佐藤賢一
    • Organizer
      日本生体エネルギー研究会 第43回討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] FRET型蛍光バイオセンサーを用いたミトコンドリア分岐鎖アミノ酸輸送体の探索2017

    • Author(s)
      中嶋瞳、吉田有希、垣塚彰、今村博臣
    • Organizer
      日本生体エネルギー研究会 第43回討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] MPTPパーキンソン病モデルにおけるATP制御薬の発症緩和効果2017

    • Author(s)
      中野将希、今村博臣、笹岡紀男、山本正道、上村紀仁、首藤敏之、渕上智弘、高橋良輔、垣塚彰
    • Organizer
      日本生体エネルギー研究会 第43回討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 出芽酵母の細胞内ATP変動を制御する仕組み2017

    • Author(s)
      高稲正勝、今村博臣、吉田知史
    • Organizer
      日本生体エネルギー研究会 第43回討論会
    • Related Report
      2017 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi