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

2013 Fiscal Year Final Research Report

• 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
• 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

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): Nishikawa, K., Fukuda, H., Abe, M., Nakanishi, K., Tazawa, Y., Yamaguchi, C., Hiradate, S., Fujii, Y., Okuda, K., Shindo, M.
  • Journal Title: Phytochemistry Volume: 93 Pages: 223-234
  • DOI: 10.1016/j.phytochem.2013.10.001
  • Peer Reviewed
• [Journal Article] Substituent effects of cis-cinnamic acid analogues as plant growth inhibitors (2013)
  • Author(s): Nishikawa, K., Fukuda, H., Abe, M., Nakanishi, K., Taniguchi, T., Nomura, T., Yamaguchi, C., Hiradate, S., Fujii, Y., Okuda, K., Shindo, M.
  • Journal Title: Phytochemistry Volume: 96 Pages: 132-147
  • DOI: 10.1016/j.fob.2013.09.007
  • 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., Shikanai, T.
  • Journal Title: FEBS, Open Bio. Volume: 7 Pages: 52-57
  • DOI: 10.1016/j.bmcl.2013.01.018
  • Peer Reviewed
• [Journal Article] Critical role of a methyl group on the gamma-lactone ring of annonaceous acetogenin in the potent inhibition of mitochondrial complex I (2013)
  • Author(s): Kojima, N., Abe, M., Suga, Y., Ohtsuki, K., Tanaka, T., Iwasaki, H., Yamashita, M., Miyoshi, H.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 23 Pages: 1217-1219
  • DOI: 10.1016/j.bmcl.2013.01.018
  • 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
  • DOI: 10.1021/tx300315
  • 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
  • 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] 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] 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
• [Remarks]
  • URL: http://www.biofunc-chem.kais.kyoto-u.ac.jp/