Paper Details
- Takeshi Ito (Institute for Genome Research, Tokushima University / Graduate School of Pharmaceutical Sciences, Tokushima University / itou.takeshi@tokushima-u.ac.jp)
- Yasuo Shinohara (Institute for Genome Research, Tokushima University / Graduate School of Pharmaceutical Sciences, Tokushima University / yshinoha@genome.tokushima-u.ac.jp)
1) Institute for Genome Research, Tokushima University , 2) Graduate School of Pharmaceutical Sciences, Tokushima University , 3) Division of Molecular Target and Gene Therapy Products, Institute for National Health Sciences , 4) Institute for Materials Chemistry and Engineering, Kyushu University
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.
