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Modification of mitochondrial fission factor, DRP1 affects the biotransformation of glucose through sulfur-containing amino acid metabolism.

Research Project

Project/Area Number 24510304
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Living organism molecular science
Research InstitutionKeio University

Principal Investigator

YAMAMOTO Takehiro  慶應義塾大学, 医学部, 講師 (50383774)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsメチル化 / ミトコンドリア / Drp1 / Gfer / 解糖系 / メチオニン代謝 / 含硫アミノ酸 / 含硫アミノ酸代謝
Outline of Final Research Achievements

Mitochondrial dynamics (fusion vs fission) have been closely linked to cell fate and homeostasis to maintain mitochondrial functions. Recent studies showed that posttranslational modifications of several mitochondrial GTPases are involved in regulation of their shape. Here, we showed evidences that mitochondrial fission factor, DRP1 (dynamin-like protein 1) and GFER (growth factor, augmenter of live regeneration) were arginine-methylated in vitro. Furthermore, artificial inhibition of methionine cycle using modified culture medium reduced the expression level of DRP1 coincident with the suppression of glycolytic flux. On the contrary, we found that activation of glycolytic flux caused mitochondrial fission through the DRP1 induction with murine macrophage differentiation model. These results suggest that changes in mitochondrial shape through the regulation of methionine metabolism might alter the balance of glucose utilization between glycolysis and oxidative phosphorylation.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (15 results)

All 2014 2013 2012 Other

All Journal Article (6 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (7 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Impacts of CD44 knockdown in cancer cells on tumor and host metabolic systems revealed by quantitative imaging mass spectrometry.2014

    • Author(s)
      Ohmura M, Hishiki T, Yamamoto T, Nakanishi T, Kubo A, Tsuchihashi K, Tamada M, Toue S, Kabe Y, Saya H and Suematsu M
    • Journal Title

      Nitric Oxide

      Volume: pii: S1089-8603 Pages: 495-499

    • DOI

      10.1016/j.niox.2014.11.005

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] メチオニン代謝の変動ががんの代謝を決める~アルギニンメチル化修飾によるがん細胞の糖代謝制御2014

    • Author(s)
      山本雄広、高野直治、石渡恭子、末松 誠
    • Journal Title

      実験医学増刊

      Volume: 32 Pages: 78-85

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Reduced methylation of PFKFB3 in cancer cells shunts glucose towards the pentose phosphate pathway.2014

    • Author(s)
      Takehiro Yamamoto, Naoharu Takano, Kyoko Ishiwata, Mitsuyo Ohmura, Yoshiko Nagahata, Tomomi Matsuura, Aki Kamata, Kyoko Sakamoto, Tsuyoshi Nakanishi, Akiko Kubo, Takako Hishiki, and Makoto Suematsu.
    • Journal Title

      Nature Communications

      Volume: 5 Issue: 1 Pages: 3480-3480

    • DOI

      10.1038/ncomms4480

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Energy management by enhanced glycolysis in G1-phase in human colon cancer cells in vitro and in vivo.2013

    • Author(s)
      Bao Y, Mukai K, Hishiki T, Kubo A, Ohmura M, Sugiura Y, Matsuura T, Nagahata Y, Hayakawa N, Yamamoto T, Fukuda R, Saya H, Suematsu M, Minamishima YA.
    • Journal Title

      Mol Cancer Res.

      Volume: 11 Issue: 9 Pages: 973-985

    • DOI

      10.1158/1541-7786.mcr-12-0669-t

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Modulation of glucose metabolism by CD44 contributes to antioxidant status and drug resistance in cancer cells.2012

    • Author(s)
      Tamada M, Nagano O, Tateyama S, Ohmura M, Yae T, Ishimoto T, Sugihara E, Onishi N, Yamamoto T, Yanagawa H, Suematsu M, and Saya H.
    • Journal Title

      Cancer Research

      Volume: 72 Pages: 1438-1448

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Carbon monoxide : Impact on remethylation and transsulfuration metabolism and its pathophysiologic implications2012

    • Author(s)
      Hishiki T, Yamamoto T, Morikawa T, Kubo A, Kajimura M, Suematsu M
    • Journal Title

      Journal of molecular medicine

      Volume: 90 Issue: 3 Pages: 245-254

    • DOI

      10.1007/s00109-012-0875-2

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] アルギニンメチル化修飾が制御するがん細胞の代謝2014

    • Author(s)
      山本雄広、高野直治、石渡恭子、末松誠
    • Organizer
      第37回日本分子生物学会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 解糖系酵素PFKFB3のメチル化修飾によるがん細胞の糖代謝制御2014

    • Author(s)
      山本雄広、高野直治、石渡恭子、大村光代、長畑善子、松浦友美、久保亜希子、菱木貴子、末松誠
    • Organizer
      第87回日本生化学会
    • Place of Presentation
      京都市
    • Year and Date
      2014-10-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] ミトコンドリアの形態変化による細胞内エネルギー代謝調節機構の解明2014

    • Author(s)
      山本雄広
    • Organizer
      第3回マトリョーシカ型生物学研究会
    • Place of Presentation
      神戸市
    • Year and Date
      2014-07-11 – 2014-07-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] 解糖系酵素PFKFB3のメチル化制御はがん細胞の酸化ストレス耐性獲得に重要である2013

    • Author(s)
      山本雄広、石渡恭子、高野直治、大村光代、菱木貴子、長畑善子、末松 誠
    • Organizer
      第86回 日本生化学会本大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] アルギニンメチル化酵素PRMT1の細胞内局在を反映した糖代謝酵素の核内メチル化機構2013

    • Author(s)
      山本雄広、石渡恭子、高野直治、大村光代、菱木貴子、長畑善子、末松 誠
    • Organizer
      第36回 日本分子生物学会本大会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Research-status Report
  • [Presentation] 一酸化炭素(CO)を介したアルギニンメチル化制御による糖代謝リモデリング機構の解明2012

    • Author(s)
      山本雄広、石渡恭子、高野直治、菱木貴子、長畑善子、末松 誠
    • Organizer
      第85回 日本生化学会大会
    • Place of Presentation
      福岡国際会議場、福岡市
    • Related Report
      2012 Research-status Report
  • [Presentation] Carbon monoxide regulates directional biotransformation of glucose via protein arginine methylation2012

    • Author(s)
      Takehiro Yamamoto, Kyoko Ishiwata, Naoharu Takano, Makoto Suematsu
    • Organizer
      第33回 内藤コンファレンス酸素生物学:酸素濃度に対する生物応答とその制御破綻による疾患」
    • Place of Presentation
      ガトーキングダム、札幌市
    • Related Report
      2012 Research-status Report
  • [Book] 酸化ストレスの医学2014

    • Author(s)
      末松 誠、山本雄広、梶村眞弓
    • Total Pages
      8
    • Publisher
      診断と治療社
    • Related Report
      2014 Annual Research Report
  • [Remarks] 慶應義塾大学医学部医化学教室ホームページ

    • URL

      http://www.gasbiology.com/

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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