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Structural analysis of mitochondrial apoptotic pore

Research Project

Project/Area Number 23657084
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

SHIMIZU Shigeomi  東京医科歯科大学, 難治疾患研究所, 教授 (70271020)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords細胞情報伝達機構 / アポトーシス / ネクローシス / ミトコンドリア / Bax / Bak / 電子顕微鏡 / 生体膜
Research Abstract

The molecular mechanism of apoptotic mitochondrial permeability increase has not been fully elucidated yet. We aimed to analyze this structure using electron and fluorescence microscopes. In this research, we found the occurrence of criste fusion and opening, outer membrane blebbing, and Bak oligomerization during apoptosis. These findings unveil structural mechanism of apoptotic mitochondrial changes.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (54 results)

All 2013 2012 2011 2010 Other

All Journal Article (20 results) (of which Peer Reviewed: 8 results) Presentation (23 results) Book (3 results) Remarks (2 results) Patent(Industrial Property Rights) (6 results) (of which Overseas: 2 results)

  • [Journal Article] Transformation of an antimicrobial peptide into a plasma membrane- permeable,mitochondria-targeted peptide via the substitution of lysine with arginine2012

    • Author(s)
      I. Nakase, S. Okumura, S. Katayama, H. Hirose, S. Pujals, H. Yamaguchi, S. Arakawa, S. Shimizu, S. Futaki
    • Journal Title

      Chemical Communication

      Volume: 48 Pages: 11097-99

    • Related Report
      2012 Final Research Report
  • [Journal Article] Hypertrophy and unconventional cell division of hepatocytes underlie liver regeneration2012

    • Author(s)
      Y. Miyaoka, K. Ebato, H. Kato, S. Arakawa, S. Shimizu, A. Miyajima
    • Journal Title

      Curr. Biol

      Volume: 22 Pages: 1166-75

    • Related Report
      2012 Final Research Report
  • [Journal Article] Shigella targets epithelial tricellular junctions to spread between cells via a noncanonicalclathrin-dependent endocytic pathway2012

    • Author(s)
      M. Fukamatsu, M. Ogawa, S. Arakawa, H.Ashida, M. Suzuki, M. Furuse, K. Nakayama, S. Shimizu, M. Kin, H. Mimuro, C. Sasakawa
    • Journal Title

      Cell Host Microbe

      Volume: 11 Pages: 325-336

    • Related Report
      2012 Final Research Report
  • [Journal Article] Involvement of Beclin 1 in the engulfment of apoptotic cells2012

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

      J. Biol. Chem

      Volume: 287 Pages: 13919-29

    • Related Report
      2012 Final Research Report
  • [Journal Article] Inhibits Vascular Endothelial Growth Factor Expression in Solid Tumor2012

    • Author(s)
      Y. Yoshioka, S. Shimizu, T. Ito, M.Taniguchi, M. Nomura, T. Nishida, Y. Sawa.
    • Journal Title

      J Surg Res

      Volume: 174 Pages: 291-297

    • Related Report
      2012 Final Research Report
  • [Journal Article] 生体におけるマイトファジーの役割2012

    • Author(s)
      清水重臣
    • Journal Title

      「実験医学」羊土社

      Volume: 30 Pages: 1390-95

    • Related Report
      2012 Final Research Report
  • [Journal Article] オートファジー細胞死の分子機構とその生体での役割2012

    • Author(s)
      清水重臣
    • Journal Title

      「実験医学」羊土社

      Volume: 30 Pages: 550-5

    • Related Report
      2012 Final Research Report
  • [Journal Article] p53 Inhibits Vascular Endothelial Growth Factor Expression in Solid Tumor.2012

    • Author(s)
      Yasuhiko Yoshioka
    • Journal Title

      Journal of Surgical Research

      Volume: 174 Issue: 2 Pages: 291-297

    • DOI

      10.1016/j.jss.2010.12.028

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Beclin 1 in the engulfment of apoptotic cells2012

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

      J.Biol.Chem.

      Volume: (epub) Issue: 17 Pages: 13919-13929

    • DOI

      10.1074/jbc.m112.348375

    • Related Report
      2012 Annual Research Report 2011 Research-status 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
  • [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] 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] Stress-activated protein kinase MKK7 regulates axon elongation in thedeveloping cerebral cortex2011

    • Author(s)
      T. Yamasaki, H. Kawasaki, S. Arakawa, K. Shimizu, S. Shimizu, O. Reiner, H. Okano, S. Nishina, N. Azuma, J.M. Penninger, T. Katada, H Nishina
    • Journal Title

      Journal ofNeuroscience

      Volume: 31 Pages: 16872-16883

    • Related Report
      2012 Final Research Report
  • [Journal Article] Spatialcoupling of mTOR and autophagy augments secretory phenotypes2011

    • Author(s)
      M. Narita, A.R.J. Young, S. Arakawa, S.A. Samarajiwa, T. Nakashima, S. Yoshida, S.K. Hong, L.S. Berry, S. Reichelt, M. Ferreira, S. Tavare, K. Inoki, S. Shimizu, M. Narita
    • Journal Title

      Science

      Volume: 332 Pages: 966-970

    • Related Report
      2012 Final Research Report
  • [Journal Article] Delayed-onset caspase-dependent massive hepatocyte apoptosis upon Fas activation in Bak/Bax-deficient mice2011

    • Author(s)
      H. Hikita, T. Takehara, T. Kodama, S. Shimizu, M. Shigekawa, A. Hosui, T. Miyagi, T. Tatsumi, H. Ishida, Li W, T. Kanto, N. Hiramatsu, S. Shimizu, Y. Tsujimoto, N. Hayashi
    • Journal Title

      Hepatology

      Volume: 54 Pages: 240-251

    • Related Report
      2012 Final Research Report
  • [Journal Article] ミトコンドリアの変化2011

    • Author(s)
      清水重臣
    • Journal Title

      「細胞死解析プロトコール」羊土社

      Pages: 108-118

    • Related Report
      2012 Final Research Report
  • [Journal Article] アポトーシスと非アポトーシス細胞死2011

    • Author(s)
      清水重臣
    • Journal Title

      「臨床血液」教育講演号

    • NAID

      10029769484

    • Related Report
      2012 Final Research Report
  • [Journal Article] Delayed-onset caspase-dependent massive hepatocyte apoptosis upon Fasactivation in Bak/Bax-deficient mice2011

    • Author(s)
      Hikita, H.
    • Journal Title

      Hepatology

      Volume: VOL. 54 Issue: 1 Pages: 240-251

    • DOI

      10.1002/hep.24305

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Spatial coupling of mTOR and autophagy augments secretory/phenotypes2011

    • Author(s)
      Masako Narita
    • Journal Title

      Science

      Volume: 332 Issue: 6032 Pages: 966-970

    • DOI

      10.1126/science.1205407

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stress-activated protein kinase MKK7 regulates axon elongation in the developing cerebral cortex.2011

    • Author(s)
      Yamasaki T, Kawasaki H, Arakawa S, Shimizu K, Shimizu S, Reiner O, Okano H, Nishina S, Azuma N, Penninger JM, Katada T, Nishina H.
    • Journal Title

      Journal of Neuroscience

      Volume: 31 Pages: 16872-16883

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Maintenance of tissue homeostasis by dying cells and autophagy2012

    • Author(s)
      清水重臣
    • Organizer
      第35回日本分子生物学会
    • Year and Date
      2012-12-13
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] 様々なストレスに対応する為に機能するオートファジー2012

    • Author(s)
      清水重臣
    • Organizer
      第16回日本統合医療学会
    • Year and Date
      2012-12-09
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] Molecular Mechanisms andPhysiological Roles of Atg5/Atg7- independent Macroautophagy2012

    • Author(s)
      Shimizu S
    • Organizer
      The 6th Symposium on Autophagy
    • Year and Date
      2012-10-30
    • Related Report
      2012 Final Research Report
  • [Presentation] Alternative Macroautophagy and Cancer2012

    • Author(s)
      清水重臣
    • Organizer
      第71回日本癌学会
    • Year and Date
      2012-09-19
    • Related Report
      2012 Final Research Report
  • [Presentation] なぜ赤血球にはミトコンドリアがないのか?~オートファジーの働き2012

    • Author(s)
      清水重臣
    • Organizer
      第3回ミトコンドリアとDDS
    • Year and Date
      2012-07-07
    • Related Report
      2012 Final Research Report
  • [Presentation] 放射線によって誘導される様々な細胞死とオートファジー2012

    • Author(s)
      清水重臣
    • Organizer
      第2回分子状水素医学シンポジウム
    • Year and Date
      2012-02-11
    • Related Report
      2012 Final Research Report
  • [Presentation] Alternative Macroautophagy and Cancer2012

    • Author(s)
      Shigeomi Shimizu
    • Organizer
      第71回日本癌学会
    • Place of Presentation
      札幌市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Molecular Mechanisms and Physiological Roles of Atg5/Atg7-independent Macroautophagy2012

    • Author(s)
      Shigeomi Shimizu
    • Organizer
      The 6th Symposium on Autophagy
    • Place of Presentation
      名護市
    • Related Report
      2012 Annual Research Report
  • [Presentation] 生体で見られる様々な細胞死とオートファジー2011

    • Author(s)
      清水重臣
    • Organizer
      第1回横断的腫瘍フォーラム
    • Year and Date
      2011-12-07
    • Related Report
      2012 Final Research Report
  • [Presentation] オートファジーを標的とした難治疾患克服への戦略2011

    • Author(s)
      清水重臣
    • Organizer
      金沢大学がん進展制御研究所セミナー
    • Year and Date
      2011-09-27
    • Related Report
      2012 Final Research Report
  • [Presentation] 様々な疾患を惹起するミトコンドリア細胞死孔の解析2011

    • Author(s)
      清水重臣
    • Organizer
      第84回日本生化学会
    • Year and Date
      2011-09-24
    • Related Report
      2012 Final Research Report 2011 Research-status Report
  • [Presentation] オートファジーと神経変性疾患病態に根ざしたALSの新規治療法開発班2011

    • Author(s)
      清水重臣
    • Organizer
      平成23年度ワークショップ
    • Year and Date
      2011-09-22
    • Related Report
      2012 Final Research Report
  • [Presentation] オートファジーを標的とした難治疾患克服への戦略2011

    • Author(s)
      清水重臣
    • Organizer
      新適塾「難病への挑戦」第7回
    • Year and Date
      2011-09-02
    • Related Report
      2012 Final Research Report
  • [Presentation] 細胞死とオートファジーのクロストーク2011

    • Author(s)
      清水重臣
    • Organizer
      日本Cell Death学会
    • Year and Date
      2011-07-29
    • Related Report
      2012 Final Research Report 2011 Research-status Report
  • [Presentation] 細胞死を司るミトコンドリア孔の解析2011

    • Author(s)
      清水重臣
    • Organizer
      過渡的複合体シンポジウム
    • Year and Date
      2011-07-21
    • Related Report
      2012 Final Research Report
  • [Presentation] Alternativemacroautophagy International Symposium2011

    • Author(s)
      Shimizu S.
    • Organizer
      Parkinson Disease and Mitophagy
    • Year and Date
      2011-06-11
    • Related Report
      2012 Final Research Report
  • [Presentation] アポトーシスと非アポトーシス細胞死2011

    • Author(s)
      清水重臣
    • Organizer
      第73回日本血液学会
    • Related Report
      2012 Final Research Report
  • [Presentation] Alternative macroautophagy2011

    • Author(s)
      Shigeomi Shimizu
    • Organizer
      Parkinson Disease and Mitophagy
    • Place of Presentation
      文京区
    • Related Report
      2011 Research-status Report
  • [Presentation] オートファジーを標的とした難治疾患克服への戦略2011

    • Author(s)
      清水重臣
    • Organizer
      新適塾「難病への挑戦」(招待講演)
    • Place of Presentation
      豊中市
    • Related Report
      2011 Research-status Report
  • [Presentation] オートファジーと神経変性疾患2011

    • Author(s)
      清水重臣
    • Organizer
      「病態に根ざしたALSの新規治療法開発班」平成23年度ワークショップ(招待講演)
    • Place of Presentation
      千代田区
    • Related Report
      2011 Research-status Report
  • [Presentation] アポトーシスと非アポトーシス細胞死2011

    • Author(s)
      清水重臣
    • Organizer
      第73回日本血液学会(招待講演)
    • Place of Presentation
      名古屋市
    • Related Report
      2011 Research-status Report
  • [Presentation] Various Types of Cell Death and Autophagy2011

    • Author(s)
      Shigeomi Shimizu
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜市
    • Related Report
      2011 Research-status Report
  • [Presentation] Various Types of CellDeath and Autophagy2010

    • Author(s)
      Shimizu S
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Book] アポトーシス調節系「分子標的薬」日本臨床2012

    • Author(s)
      清水重臣
    • Related Report
      2012 Final Research Report
  • [Book] 細胞死解析プロトコール2011

    • Author(s)
      清水重臣
    • Total Pages
      223
    • Publisher
      羊土社
    • Related Report
      2011 Research-status Report
  • [Book] Mammalian autophagy can occur through an Atg5/Atg7- independent pathway. AUTOPHAGY: Cancer, Other Pathologies

    • Author(s)
      S. Shimizu, S. Arakawa, Y. Nishida, H. Yamaguchi, T. Yoshida
    • Publisher
      Inflammation, Immunity, and Infection(印刷中)
    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2012 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
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] ベンゾチオフェン化合物、該化合物を有効成分とするオルタナティブオートファジー誘導剤及び抗癌剤、並びに抗癌活性を有する化合物をスクリーニングするための 方法2013

    • Inventor(s)
      Shigeomi SHIMIZU, Takamitsu HOSOYA, Michiko MUROHASHI, Suguru YOSHIDA
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学
    • Filing Date
      2013-02-07
    • Related Report
      2012 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] ベンゾチオフェン化合物、該化合物を有効成分とするオルタナティブオートファジー誘導剤及び抗癌剤、並びに抗癌活性を有する化合物をスクリーニングするための方法2013

    • Inventor(s)
      清水重臣、室橋道子、細谷孝充、吉田優
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-02-07
    • Related Report
      2012 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 抗癌活性を有する化合物をスクリーニングするための方法2012

    • Inventor(s)
      清水重臣、室橋道子
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学
    • Industrial Property Number
      2012-026377
    • Filing Date
      2012-02-09
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] ベンゾチオフェン化合物、並びに該化合物を有効成分とするオルタナティブオートファジー誘導剤及び抗癌剤2012

    • Inventor(s)
      清水重臣、細谷孝充、室橋道子、吉田優
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学出願
    • Industrial Property Number
      2012-026373
    • Filing Date
      2012-02-09
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] 抗癌活性を有する化合物をスクリーニングするための方法2012

    • Inventor(s)
      清水重臣 室橋道子
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学
    • Industrial Property Number
      2012-026377
    • Filing Date
      2012
    • Related Report
      2011 Research-status Report
  • [Patent(Industrial Property Rights)] ベンゾチオフェン化合物、並びに該化合物を有効成分とするオルタナティブオートファジー誘導剤及び抗癌剤2012

    • Inventor(s)
      清水重臣 室橋道子 細谷孝充 吉田満
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学
    • Industrial Property Number
      2012-026373
    • Filing Date
      2012
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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