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Three classes of ubiquinone analogs regulate the mitochondrial permeability transition pore through a common site.

Abstract : To identify the structural features required for regulation of the mitochondrial permeability transition pore (PTP) by ubiquinone analogs (Fontaine, E., Ichas, F., and Bernardi, P. (1998) J. Biol. Chem. 40, 25734-25740), we have carried out an analysis with quinone structural variants. We show that three functional classes can be defined: (i) PTP inhibitors (ubiquinone 0, decylubiquinone, ubiquinone 10, 2,3-dimethyl-6-decyl-1,4-benzoquinone, and 2,3,5-trimethyl-6-geranyl-1,4-benzoquinone); (ii) PTP inducers (2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone and 2,5-dihydroxy-6-undecyl-1,4-benzoquinone); and (iii) PTP-inactive quinones that counteract the effects of both inhibitors and inducers (ubiquinone 5 and 2,3,5-trimethyl-6-(3-hydroxyisoamyl)-1,4-benzoquinone) . The structure-function correlation indicates that minor modifications in the isoprenoid side chain can turn an inhibitor into an activator, and that the methoxy groups are not essential for the effects of quinones on the PTP. Since the ubiquinone analogs used in this study have a similar midpoint potential and decrease mitochondrial production of reactive oxygen species to the same extent, these results support the hypothesis that quinones modulate the PTP through a common binding site rather than through oxidation-reduction reactions. Occupancy of this site can modulate the PTP open-closed transitions, possibly through secondary changes of the PTP Ca(2+) binding affinity.
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https://www.hal.inserm.fr/inserm-00390044
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Submitted on : Saturday, May 30, 2009 - 3:44:02 PM
Last modification on : Friday, November 25, 2022 - 7:07:32 PM

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Ludivine Walter, Véronique Nogueira, Xavier M Leverve, Marie-Paule Heitz, Paolo Bernardi, et al.. Three classes of ubiquinone analogs regulate the mitochondrial permeability transition pore through a common site.. Journal of Biological Chemistry, 2000, 275 (38), pp.29521-7. ⟨10.1074/jbc.M004128200⟩. ⟨inserm-00390044⟩

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