Suramin Inhibits Mitochondrial ADP/ATP Carrier, Not Only from the Cytosolic Side But Also from the Matrix Side, of the Mitochondrial Inner Membrane

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  • Fujiwara Yoshinobu
    Institute for Genome Research, Tokushima University Graduate School of Pharmaceutical Sciences, Tokushima University
  • Ito Takeshi
    Institute for Genome Research, Tokushima University Graduate School of Pharmaceutical Sciences, Tokushima University
  • Toiyama Atsumi
    Institute for Genome Research, Tokushima University Graduate School of Pharmaceutical Sciences, Tokushima University
  • Yamamoto Takenori
    Institute for Genome Research, Tokushima University Division of Molecular Target and Gene Therapy Products, Institute for National Health Sciences
  • Yamazaki Naoshi
    Graduate School of Pharmaceutical Sciences, Tokushima University
  • Shindo Mitsuru
    Institute for Materials Chemistry and Engineering, Kyushu University
  • Shinohara Yasuo
    Institute for Genome Research, Tokushima University Graduate School of Pharmaceutical Sciences, Tokushima University

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Abstract

<p>Suramin was earlier reported to show inhibitory effects on the mitochondrial ADP/ATP carrier. However, two important questions, i) whether it shows a specific inhibition of the ADP/ATP carrier when applied to isolated mitochondria, and ii) whether it inhibits the mitochondrial ADP/ATP carrier only from the cytosolic side or from the matrix side, as has been observed with its canonical inhibitors of carboxyatractyloside or bongkrekic acid, remain to be answered. In the present study, we sought exact answers to these questions. As for the first question, suramin showed certain inhibitory effects on the mitochondrial respiratory chain; and at a concentration of 25 μM it showed strong inhibition of the mitochondrial ADP/ATP carrier. This property was due to its weaker inhibitory effects on the mitochondrial ADP/ATP carrier than those of carboxyatractyloside or bongkrekic acid. As for the second question, suramin inhibited the ADP/ATP carrier from both sides of the mitochondrial inner membrane. Thus, suramin was concluded to be utilizable as a new type of inhibitor for the ADP/ATP carrier; but we must pay attention to its side-effects, especially when it is applied to whole mitochondria.</p>

Journal

  • BPB Reports

    BPB Reports 4 (3), 92-97, 2021

    The Pharmaceutical Society of Japan

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