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

Biochim Biophys Acta. 1989 Aug 3;975(3):325-9. doi: 10.1016/s0005-2728(89)80339-1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Almitrine
  • Cell Division / drug effects
  • Energy Metabolism / drug effects
  • Growth Inhibitors / pharmacology*
  • Kinetics
  • Mitochondria / drug effects
  • Mitochondria / enzymology*
  • Mitochondria / metabolism
  • Oxidative Phosphorylation
  • Piperazines / pharmacology*
  • Proton-Translocating ATPases / antagonists & inhibitors*
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Uncoupling Agents / pharmacology


  • Growth Inhibitors
  • Piperazines
  • Uncoupling Agents
  • Adenosine Triphosphate
  • Almitrine
  • Proton-Translocating ATPases