A ubiquinone-binding site regulates the mitochondrial permeability transition pore

Eric Fontaine, François Ichas, Paolo Bernardi
J. Biol. Chem.. 1998-10-02; 273(40): 25734-25740
DOI: 10.1074/jbc.273.40.25734

Read on PubMed

We have investigated the regulation of the mitochondrial permeability transition
pore (PTP) by ubiquinone analogues. We found that the Ca2+-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 Pi 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.


Know more about