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Elucidation of the role of alternative autophagy in hemophagocytotic syndrome

Research Project

Project/Area Number 24689020
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Human pathology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

ARAKAWA Satoko  東京医科歯科大学, 難治疾患研究所, 助教 (90415159)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥27,040,000 (Direct Cost: ¥20,800,000、Indirect Cost: ¥6,240,000)
Fiscal Year 2013: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Fiscal Year 2012: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
Keywordsオートファジー / マイトファジー / 赤血球 / 血球分化 / ミトコンドリア / 血球貪食症候群
Research Abstract

Macroautophagy degrades subcellular constituents and some evidences indicate that it is involved in elimination of some organelles. In erythrocyte differentiation, mitochondria are removed from reticulocytes and it has been suggested that macroautophagy is required for it. Although it is believed that Atg5 and Atg7 are indispensable for macroautophagy, their role in this process is controversial. Recently, we discovered that mammalian cells possess Atg5/Atg7-independent macroautophagy as well as Atg5/Atg7-dependent macroautophagy and Ulk1 regulates the former process. We hypothesized that Ulk1-mediated Atg5/Atg7-independent macroautophagy is involved in the elimination of mitochondria from reticulocytes. In this study, we demonstrated the removal of mitochondria in Ulk1-deficient erythrocytes was impaired. Furthermore, Ulk-1 deficient embryo becomes anemia. This would be attributed to the more susceptibility of the erythrocytes to the apoptosis and the engulfment by macrophage.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • Research Products

    (24 results)

All 2014 2013 2012 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) Book (3 results) Remarks (3 results)

  • [Journal Article] Ulk1-mediated Atg5-independent macroautophagy mediates elimination of mitochondria from embryonic reticulocytes2014

    • Author(s)
      S. Honda, S. Arakawa, Y. Nishida, H. Yamaguchi, E. Ishii, S. Shimizu.
    • Journal Title

      Nature communications

      Volume: 5 Issue: 1 Pages: 4004-4004

    • DOI

      10.1038/ncomms5004

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Ulk1-mediated Atg5-independent macroautophagy mediates elimination of mitochondria from embryonic reticulocytes2014

    • Author(s)
      Honda S, Arakawa S, Nishida Y, Yamaguchi H, Ishii E, Shimizu S
    • Journal Title

      Nature Commun. in press

      Volume: -

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alternative Macroautophagy and Mitophagy2014

    • Author(s)
      S. Shimizu, S. Honda, S. Arakawa, H. Yamaguchi
    • Journal Title

      Int. J. Biochem. Cell Biol.

      Volume: 50 Pages: 64-66

    • DOI

      10.1016/j.biocel.2014.02.016

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Autophagic Cell Death and Cancer.2014

    • Author(s)
      S. Shimizu, T. Yoshida, M. Tsujioka, S. Arakawa.
    • Journal Title

      Int J Mol Sci.

      Volume: 15 Issue: 2 Pages: 3145-3153

    • DOI

      10.3390/ijms15023145

    • NAID

      40019721683

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of epithelial cell death by Bcl-2 improved chronic colitis in IL10 KO mice2013

    • Author(s)
      T. Mizushima, S. Arakawa, Y. Sanada, I. Yoshino, D. Miyazaki, H. Urushima, Y. Tsujimoto, T. Ito, S. Shimizu
    • Journal Title

      Am J Pathol.

      Volume: 183 Issue: 6 Pages: 1936-1944

    • DOI

      10.1016/j.ajpath.2013.08.012

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transformation of an antimicrobial peptide into a plasma membrane-permeable, mitochondria-targeted peptide via the substitution of lysine with arginine2012

    • Author(s)
      Ikuhiko Nakase, Shinya Okumura, Sayaka Katayama, Hisaaki Hirose, Silvia Pujals, Hirofumi Yamaguchi, Satoko Arakawa, Shigeomi Shimizu, Shiroh Futaki
    • Journal Title

      Chemical Communications

      Volume: 48 Issue: 90 Pages: 11097-11099

    • DOI

      10.1039/c2cc35872g

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypertrophy and unconventional cell division of hepatocytes underlie liver regeneration.2012

    • Author(s)
      Yuichiro Miyaoka
    • Journal Title

      Current Biology

      Volume: 22 Issue: 13 Pages: 1166-1175

    • DOI

      10.1016/j.cub.2012.05.016

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of beclin 1 in engulfment of apoptotic cells.2012

    • Author(s)
      Konishi A, Arakawa S, Yue Z, and Shimizu S.
    • Journal Title

      J Biol Chem

      Volume: 287(17) Pages: 13919-13929

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Shigella targets epithelial tricellular junctions to spread between cells via a noncanonical clathrin-dependent endocytic pathway.2012

    • Author(s)
      Makoto Fukumatsu
    • Journal Title

      Cell Host & Microbe

      Volume: 11 Issue: 4 Pages: 325-336

    • DOI

      10.1016/j.chom.2012.03.001

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Analysis of programmed cell death during mice development2013

    • Author(s)
      荒川聡子、吉野育代、辻本賀英、清水重臣
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] 中心体数の制御機構の解明2013

    • Author(s)
      荒川聡子、本田真也、渡辺雄一郎、小西昭充、清水重臣
    • Organizer
      新学術研究領域「シリア・中心体による生体情報フローの制御」第二回領域会議
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] Analysis of programmed cell death during interdigital web development2013

    • Author(s)
      荒川聡子、吉野育代、辻本賀英、清水重臣
    • Organizer
      第22回日本Cell death学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] A Cell-Death Inducing Chemical Targets on the Centrosome2013

    • Author(s)
      Satoko Arakawa, Yuichiro Watanabe, Michiko Murohashi, Shinya Honda, Akimitsu Konishi, Hirofumi Yamaguchi and Shigeomi Shimizu
    • Organizer
      The 25th CDB Meeting Cilia and Centrosomes, from Fertilization to Cancer
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] Analysis of programmed cell death during mice development2013

    • Author(s)
      Arakawa S, Yoshino I, Tsujimoto Y, Shimizu S
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸(ポートアイランド)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Analysis of programmed cell death during interdigital web development2013

    • Author(s)
      Arakawa S, Yoshino I, Tsujimoto Y, Shimizu S
    • Organizer
      第22回日本Cell death学会学術集会
    • Place of Presentation
      京都(京都大学芝蘭会館)
    • Related Report
      2013 Annual Research Report
  • [Presentation] A Cell-Death Inducing Chemical Targets on the Centrosome2013

    • Author(s)
      Arakawa S, Watanabe Y, Murohashi M, Honda S, Konishi A, Yamaguchi H and Shimizu S
    • Organizer
      The 25th CDB Meeting Cilia and Centrosomes, from Fertilization to Cancer
    • Place of Presentation
      神戸(理化学研究所)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 中心体数の制御機構の解明2013

    • Author(s)
      荒川聡子、本田真也、渡辺雄一郎、小西昭充、清水重臣
    • Organizer
      新学術研究領域「シリア・中心体による生体情報フローの制御」第二回領域会議
    • Place of Presentation
      名古屋(ルブラ王山)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Discovery of Atg5-independent alternative macroautop hagy in yeast and its morphological analysis2012

    • Author(s)
      Arakawa S, Yamaguchi H, Kanaseki T,and Shimizu S.
    • Organizer
      分子生物学会年会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-11
    • Related Report
      2012 Annual Research Report
  • [Book] Alternative macroautophagy and mitophagy (Int J Biochem Cell Biol . 50)2014

    • Author(s)
      Shimizu S, Honda S, Arakawa S, Yamaguchi H
    • Publisher
      (doi : 10.1016/j.biocel.2014.02.016)
    • Related Report
      2013 Final Research Report
  • [Book] Autophagic cell death and cancer (Int J Mol Sci. 15(2))2014

    • Author(s)
      Shimizu S, Yoshida T, Tsujioka M, Arakawa S
    • Publisher
      (doi :10.3390/ijms15023145)
    • Related Report
      2013 Final Research Report
  • [Book] オートファジー細胞死.医学のあゆみVol.246, No. 52013

    • Author(s)
      荒川聡子、清水重臣
    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://www.tmd.ac.jp/mri/pcb/index.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 東京医科歯科大学 難治疾患研究所 病態細胞生物学分野 ホームページ

    • URL

      http://www.tmd.ac.jp/mri/pcb/index.html

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.tmd.ac.jp/mri/pcb/index.html

    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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