Molecular mechanisms of the formation and the dissociation of the cytochrome c-cardiolipin complex

• Project/Area Number: 24780112
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bioproduction chemistry/Bioorganic chemistry
• Research Institution: Kyoto University
• Principal Investigator: ABE Masato 京都大学, (連合)農学研究科(研究院), 助教 (30543425)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: カルジオリピン / シトクロムｃ / ミトコンドリア / アポトーシス / リン脂質 / シトクロムC / シトクロムc / リポソーム

Research Abstract

Cardiolipin (CL) is a unique phospholipid in mitochondrial membranes with diverse biological functions. Induction of the peroxidase activity of cyt c by CL binding in the presence of hydrogen peroxide has been thought to be a key event in early apoptosis stage.
We synthesized a series of oxidized CLs in which four acyl chains were oxidized in different patterns. All oxidized CLs elicited strong inducing ability of the peroxidase activity of cyt c. A difference in the oxidized position including the number of OH group did not affect the inducing ability. Our results do not support a currently accepted notion that hydrophobic interaction between the acyl chains of CL and cyt c is critical for the formation of specific CL-cyt c complex and consequent induction of the peroxide activity.
Moreover, we synthesized some photoreactive CLs. By photoaffinity labeling experiments, the labeled peptide was detected by attaching a biotin to the incorporated ethynyl group by click chemistry.

Research Products

• [Journal Article] Design and Synthesis of Conformationally Constrained Analogues of cis-Cinnamic Acid and Evaluation of Their Plant Growth Inhibitory Activity (2013)
  • Author(s): Keisuke Nishikawa, Hiroshi Fukuda, Masato Abe, Kazunari Nakanishi, Yuta Tazawa, Chihiro Yamaguchi, Syuntaro Hiradate, Yoshiharu Fujii, Katsuhiro Okuda, Mitsuru Shindo
  • Journal Title: Phytochemistry Volume: 96 Pages: 223-234
  • DOI: 10.1016/j.phytochem.2013.10.001
  • Peer Reviewed
• [Journal Article] Antimycin A-like molecules inhibit cyclic electron transport around photosystem I in ruptured chloroplasts (2013)
  • Author(s): Taira Y., Okegawa Y., Sugimoto K., Abe M., Miyoshi H. and Shikanai T
  • Journal Title: FEBS Open Bio. Volume: 3 Issue: 1 Pages: 406-410
  • DOI: 10.1016/j.fob.2013.09.007
  • Peer Reviewed / Open Access
• [Journal Article] Critical role of a methyl group on theγ-lactone ring of annonaceous acetogenins in the potent inhibition of mitochondrial complex I (2013)
  • Author(s): Naoto Kojima, Masato Abe, Yuki Suga, Kazufumi Ohtsuki, Tetsuaki Tanaka, Hiroki Iwasaki, Masayuki Yamashita, Hideto Miyoshi
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 23 Issue: 5 Pages: 1217-1219
  • DOI: 10.1016/j.bmcl.2013.01.018
  • Peer Reviewed
• [Journal Article] Substituent effects of cis-cinnamic acid analogues as plant growh inhibitors (2013)
  • Author(s): Keisuke Nishikawa, Hiroshi Fukuda, Masato Abe, Kazunari Nakanishi, Tomoya Taniguchi, Takashi Nomura, Chihiro Yamaguchi, Syuntaro Hiradate, Yoshiharu Fujii, Katsuhiro Okuda, Mitsuru Shindo
  • Journal Title: Phytochemistry Volume: 96 Pages: 132-147
  • DOI: 10.1016/j.phytochem.2013.08.013
  • Peer Reviewed
• [Journal Article] Molecular design, synthesis, and evaluation of novel potent apoptosis inhibitors inspired from bongkrekic acid (2012)
  • Author(s): Okuda, K., Hasui, K., Abe, M., Matsumoto, K., Shindo, M.
  • Journal Title: Chem. Res. Toxic. Volume: 25 Pages: 2253-2260
  • Peer Reviewed
• [Journal Article] Key structural features of cis-cinnamic acid as an allelochemical (2012)
  • Author(s): Abe, M., Nishikawa, K., Fukuda, H., Nakanishi, K., Tazawa, Y., Taniguchi, T., Park, K., Hiradate, S., Fujii, Y., Okuda, K., Shindo, M.
  • Journal Title: Phytochemistry Volume: 84 Pages: 56-67
  • Peer Reviewed
• [Journal Article] Molecular design, synthesis, and evaluation of novel potent apoptosis inhibitors inspired from bongkrekic acid (2012)
  • Author(s): Okuda, K., Hasui, K., Abe, M., Matsumoto, K., Shindo, M
  • Journal Title: Chem. Res. Toxicol Volume: 25 Issue: 10 Pages: 2253-2260
  • DOI: 10.1021/tx300315h
  • Peer Reviewed
• [Journal Article] Key Structural Features of cis-Cinnamic Acid as an Allelochemical (2012)
  • Author(s): Masato Abe, Keisuke Nishikawa, Hiroshi Fukuda, Kazunari Nakanishi, Yuta Tazawa, Tomoya Taniguchi, So-young Park, Syuntaro Hiradate, Yoshiharu Fujii, Katsuhiro Okuda, Mitsuru Shindo
  • Journal Title: Phytochemistry Volume: 84 Pages: 56-67
  • DOI: 10.1016/j.phytochem.2012.08.001
  • Peer Reviewed
• [Presentation] シトクロムc-カルジオリピン複合体のペルオキシダーゼ活性誘導の分子機構 (2014)
  • Author(s): 三木裕子、安部真人、三芳秀人
  • Organizer: 日本農芸化学会2014年度大会
  • Place of Presentation: 明治大学
  • Year and Date: 2014-03-29
• [Presentation] リン脂質カルジオリピンのシトクロムcに対する結合部位の同定 (2014)
  • Author(s): 小坂亜弓、田邊有貴恵、安部真人、三芳秀人
  • Organizer: 日本農芸化学会2014年度大会
  • Place of Presentation: 明治大学
  • Year and Date: 2014-03-29
• [Presentation] リン脂質カルジオリピンのシトクロムcへの結合部位の同定 (2014)
  • Author(s): 小坂亜弓、田邊有貴恵、安部真人、三芳秀人
  • Organizer: 日本農薬学会第39会大会
  • Place of Presentation: 京都大学
  • Year and Date: 2014-03-14
• [Presentation] カルジオリピン-シトクロムc複合体のペルオキシダーゼ誘導の分子機構 (2014)
  • Author(s): 三木裕子、安部真人、三芳秀人
  • Organizer: 日本農薬学会第39会大会
  • Place of Presentation: 京都大学
  • Year and Date: 2014-03-14
• [Presentation] リン脂質カルジオリピンのシトクロムｃへの結合部位の同定 (2014)
  • Author(s): 小坂亜弓、田邊有紀貴恵、安部真人、三芳秀人
  • Organizer: 日本農薬学会第39回大会
  • Place of Presentation: 京都大学農学部
• [Presentation] カルジオリピン-シトクロムｃ複合体のペルオキシダーゼ誘導の分子機構 (2014)
  • Author(s): 三木裕子、安部真人、三芳秀人
  • Organizer: 日本農薬学会第39回大会
  • Place of Presentation: 京都大学農学部
• [Presentation] リン脂質カルジオリピンのシトクロムｃに対する結合部位の同定 (2014)
  • Author(s): 小坂亜弓、田邊有貴恵、安部真人、三芳秀人
  • Organizer: 日本農芸化学会2014年度大会
  • Place of Presentation: 明治大学農学部
• [Presentation] シトクロムｃ-カルジオリピン複合体のペルオキシダーゼ活性誘導の分子機構 (2014)
  • Author(s): 三木裕子、安部真人、三芳秀人
  • Organizer: 日本農芸化学会2014年度大会
  • Place of Presentation: 明治大学農学部
• [Presentation] Synthesis and characterization of photoaffinity probes of cardiolipin as a key player of the induction of peroxidase activity of cytochrome c (2013)
  • Author(s): Abe, M., Kosaka, A., Nakano, M., Miyoshi, H.
  • Organizer: Gordon Research
  • Place of Presentation: New Hampshire, USA
  • Year and Date: 2013-06-25
• [Presentation] カルジオリピン-シトクロムc複合体形成の分子機構解明 (2013)
  • Author(s): 安部真人、中野正晶、小坂亜弓、三芳秀人
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 東北大学
  • Year and Date: 2013-03-26
• [Presentation] カルジオリピン‐シトクロムc複合体形成の分子機構解明 (2013)
  • Author(s): 安部 真人、中野 正晶、小坂 亜弓、三芳 秀人
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 東北大学（仙台）
• [Presentation] シトクロムc-カルジオリピン複合体形成によるペルオキシダーゼ活性誘導の分子機構 (2012)
  • Author(s): 安部真人、中野正晶、三芳秀人
  • Organizer: 第85会日本生化学会大会
  • Place of Presentation: マリンメッセ福岡
  • Year and Date: 2012-12-14
• [Presentation] Structural factors of cardiolipin required for induction of peroxidase activity of cytochrome c-cardiolipin complex (2012)
  • Author(s): Abe, M., Nakano, M., Miyoshi, H.
  • Organizer: 17^<th> European Bioenergetics Conference
  • Place of Presentation: freiburg
  • Year and Date: 2012-09-17
• [Presentation] シトクロムc－カルジオリピン複合体形成によるペルオキシダーゼ活性誘導の分子機構 (2012)
  • Author(s): 安部 真人、中野 正晶、三芳 秀人
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: マリンメッセ福岡（福岡市）
• [Presentation] Structural Factors of Cardiolipin Required for Induction of Peroxidase Activity of Cytochrome c―Cardiolipin Complex (2012)
  • Author(s): M. Abe, M. Nakano, H. Miyoshi
  • Organizer: 17th European Bioenergetics Conference 2012
  • Place of Presentation: フライブルク大（ドイツ）
• [Remarks]
  • URL: http://www.biofunc-chem.kais.kyoto-u.ac.jp/
• [Remarks] 京都大学大学院農学研究科応用生命科学専攻生物機能制御化学研究室
  • URL: http://www.biofunc-chem.kais.kyoto-u.ac.jp/
• [Remarks] 京都大学大学院農学研究科応用生命科学専攻 生物機能制御化学研究室
  • URL: http://www.biofunc-chem.kais.kyoto-u.ac.jp/