Elucidation of mechanism for cytochrome c dessociation based on fine synthesis of phospholipid cardiolipin peroxide

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K05847
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38040:Bioorganic chemistry-related
• Research Institution: Ehime University
• Principal Investigator: ABE Masasto 愛媛大学, 農学研究科, 准教授 (30543425)
• Co-Investigator(Kenkyū-buntansha): 河崎 悠也 九州大学, 先導物質化学研究所, 学術研究員 (00781999)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: カルジオリピン / ミトコンドリア / アポトーシス / 脂質過酸化物

Outline of Final Research Achievements

Phospholipid cardiolipin, which is involved in both mitochondrial-mediated ATP production and apoptosis, releases cytochrome c upon induction to peroxide under oxidative stress conditions. However, in the cardiolipin peroxidation reaction, the component leading to the release of cytochrome c has not been identified because the secondary oxidation proceeds immediately after the cardiolipin peroxide is generated. Therefore, in this study, we aimed to achieve total synthesis of cardiolipin peroxide and to realize interaction analysis with cytochrome c. So far, we have completed selective chemical synthesis of two isomers of cardiolipin peroxide and succeeded in overcoming the most difficult task. Currently, further evaluation of affinity with cytochrome c is underway.

Free Research Field

生物有機化学

Academic Significance and Societal Importance of the Research Achievements

本研究では前例のない過酸化カルジオリピンの立体選択的な全合成を達成することができた。このことは、他の種々のリン脂質についても応用が可能である。事実、既に過酸化ホスファチジルグリセロールの全合成も達成しており、発展的な共同研究から新たな炎症メディエーターの可能性を見出すことに繋がった。また、本研究の合成手法を基盤技術として、英国ＵＣＬとの国際共同研究にも発展しており、機能性脂質の開発も進めている。