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

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Rigoulet M, Ouhabi R, Leverve X, Putod-Paramelle F, Guerin B

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

Biochim Biophys Acta. 1989 Aug 3;975(3):325-9.

PubMed ID

2527061 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Almitrine	Sodium/potassium-transporting ATPase subunit alpha-1	Protein	Humans	Yes	Binder	Details