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A Ubiquinone-binding Site Regulates the Mitochondrial Permeability Transition Pore *

Journal of Biological Chemistry, ISSN: 0021-9258, Vol: 273, Issue: 40, Page: 25734-25740
1998
  • 237
    Citations
  • 0
    Usage
  • 90
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    237
    • Citation Indexes
      235
    • Clinical Citations
      1
      • PubMed Guidelines
        1
    • Policy Citations
      1
      • Policy Citation
        1
  • Captures
    90

Article Description

We have investigated the regulation of the mitochondrial permeability transition pore (PTP) by ubiquinone analogues. We found that the Ca 2+ -dependent PTP opening was inhibited by ubiquinone 0 and decylubiquinone, whereas all other tested quinones (ubiquinone 5, 1,4-benzoquinone, 2-methoxy-1,4-benzoquinone, 2,3-dimethoxy-1,4-benzoquinone, and 2,3-dimethoxy-5,6-dimethyl-1,4-benzoquinone) were ineffective. Pore inhibition was observed irrespective of the method used to induce the permeability transition (addition of P i or atractylate, membrane depolarization, or dithiol cross-linking). Inhibition of PTP opening by decylubiquinone was comparable with that exerted by cyclosporin A, whereas ubiquinone 0 was more potent. Ubiquinone 5, which did not inhibit the PTP per se, specifically counteracted the inhibitory effect of ubiquinone 0 or decylubiquinone but not that of cyclosporin A. These findings define a ubiquinone-binding site directly involved in PTP regulation and indicate that different quinone structural features are required for binding and for stabilizing the pore in the closed conformation. At variance from all other quinones tested, decylubiquinone did not inhibit respiration. Our results define a new structural class of pore inhibitors and may open new perspectives for the pharmacological modulation of the PTP in vivo.

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