Carboxyatractylate inhibits the uncoupling effect of free fatty acids

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The ATP/ADP-antiporter inhibitors and ADP decrease the palmitate-induced stimulation of the mitochondrial respiration in the controlled state. The degree of inhibition decreases in the order: carboxyatractylate > bongkrekic acid, palmitoyl-CoA, ADP > atractylate. GDP is ineffective. The inhibiting concentration of carboxyatractylate coincides with this arresting the state 3 respiration. Carboxyatractylate inhibition decreases when the palmitate concentration increases. Stimulation of controlled respiration by FCCP or gramicidin D at any concentration of these uncouplers is carboxyatractylate-resistant, whereas that by low concentrations of DNP is partially suppressed by carboxyatractylate. These data together with observations that palmitate does not increase H+ conductance in bilayer phospholipid membranes and in cytochrome oxidase-asolectin proteoliposomes indicate that the ATP/ADP-antiporter is somehow involved in the uncoupling by low concentrations of fatty acids (or DNP), whereas that by FCCP and gramicidin D is due to their effect on the phospholipid bilayer. It is suggested that the antiporter facilitates translocation of palmitate anion across the mitochondrial membrane. © 1988.




Andreyev, A. Y., Bondareva, T. O., Dedukhova, V. I., Mokhova, E. N., Skulachev, V. P., & Volkov, N. I. (1988). Carboxyatractylate inhibits the uncoupling effect of free fatty acids. FEBS Letters, 226(2), 265–269.

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