Almitrine, a new kind of energy-transduction inhibitor acting on mitochondrial ATP synthase.

Abstract : At low concentrations, almitrine inhibits yeast cell multiplication by acting on oxidative metabolism. Studies on isolated mitochondria display the following features: (i) almitrine inhibits ATPase activity and decreases ATP/O ratio during oxidative phosphorylation; (ii) no direct effect on respiration can be evidenced; (iii) ATP/O value decreases without any change in the magnitude of delta p; (iv) the higher the ATP synthesis and respiratory fluxes, the larger is the decrease in ATP/O ratio induced by almitrine. These results indicate that almitrine does not act as a classical protonophoric uncoupler nor as previously studied non protonophoric uncouplers (e.g., general anesthetics). Our data show a direct inhibitory effect of almitrine on ATPase-ATP synthase complex. But, in contrast to the classical inhibitors of this complex, almitrine decreases the ATP/O ratio in a flux-dependent manner. Thus, almitrine could induce either an intrinsic uncoupling of H+/-ATPase (i.e., slip in this proton pump) or a change in the mechanistic H+/ATP stoichiometry at the ATPase level.
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Article dans une revue
Biochimica et Biophysica Acta - Molecular Cell Research, Elsevier, 1989, 975 (3), pp.325-9
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Soumis le : lundi 1 juin 2009 - 14:41:09
Dernière modification le : mercredi 7 novembre 2018 - 16:07:41

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  • HAL Id : inserm-00390277, version 1
  • PUBMED : 2527061

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Michel Rigoulet, Rachid Ouhabi, Xavier Leverve, Florence Putod-Paramelle, Bernard Guérin. Almitrine, a new kind of energy-transduction inhibitor acting on mitochondrial ATP synthase.. Biochimica et Biophysica Acta - Molecular Cell Research, Elsevier, 1989, 975 (3), pp.325-9. 〈inserm-00390277〉

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