The Mechanisms of the Release of Cytochrome c from Mitochondria Revealed by Proteomics Analysis

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  • Yamamoto Takenori
    Institute for Genome Research, University of Tokushima
  • Yamada Akiko
    Institute of Health Biosciences, University of Tokushima
  • Yoshimura Yuya
    Institute for Genome Research, University of Tokushima Faculty of Pharmaceutical Science, University of Tokushima
  • Terada Hiroshi
    Faculty of Pharmaceutical Sciences, Tokyo University of Science
  • Shinohara Yasuo
    Institute for Genome Research, University of Tokushima Faculty of Pharmaceutical Science, University of Tokushima

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Other Title
  • プロテオミクスで解き明かすミトコンドリアからのシトクロムc放出機構
  • プロテオミクス デ トキアカス ミトコンドリア カラ ノ シトクロム c ホウシュツ キコウ

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Abstract

  Mitochondrial permeability transition (PT) is the phenomenon in which the mitochondrial inner membrane becomes permeable to various solutes and ions. When PT is induced by Ca2+, cytochrome c is released from mitochondria into the cytosol where it then triggers subsequent steps of programmed cell death, apoptosis. Thus, the proteins that regulate PT and cytochrome c release could become druggable targets for various diseases. However, the mechanisms of PT and the release of cytochrome c have not yet been revealed. We previously showed that valinomycin, a potassium selective ionophore, also caused release of cytochrome c from mitochondria without inducing PT. This result indicates that cytochrome c could be released from mitochondria with or without induction of PT. In this study, to understand the difference of effects of valinomycin and Ca2+ on mitochondria, we examined what protein species are released from valinomycin- and Ca2+-treated mitochondria by LC-MS/MS. As a result, only the proteins located in the intermembrane space were found to be released from valinomycin-treated mitochondria, while those in both the intermembrane space and in the matrix were released from Ca2+-treated mitochondria. Furthermore, the protein releases by each reagent occurred not selectively but in a concentration-dependent manner. Based on these results, the permeabilization effects of Ca2+ and valinomycin on the inner and outer mitochondrial membranes are discussed.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 132 (10), 1099-1104, 2012-10-01

    The Pharmaceutical Society of Japan

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