The Anion-Carrier Mediated Uncoupling Effect of Dicarboxylic Fatty Acids in Liver Mitochondria Depends on the Position of the Second Carboxyl Group

O. V. Markova^1*, D. I. Bondarenko², and V. N. Samartsev^1,3

¹Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119899 Russia; fax: (095) 939-3181

²Bach Institute of Biochemistry, Russian Academy of Sciences, Leninskii pr. 33, Moscow, 117071 Russia; fax: (095) 954-2732

³Mari State University, pl. Lenina 1, Yoshkar-Ola, 424001 Russia; fax: (362-25) 5-458

^* To whom correspondence should be addressed.

Received June 22, 1998; Revision received December 4, 1998

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Effects of dicarboxylic fatty acids with varying positions of the carboxyl groups on respiration and membrane potential of liver mitochondria were studied. Tetradecylmalonic acid (a fatty acid with two carboxyl groups in the alpha-position) efficiently uncoupled oxidative phosphorylation similarly to palmitic acid with the same number of carbon atoms. Similarly to the uncoupling by palmitic acid, the coupling effects of carboxyatractylate and glutamate changed reciprocally with changes in pH of the incubation medium: on increasing the pH from 7.0 to 7.8, the coupling effect of carboxyatractylate increased and that of glutamate decreased. A dicarboxylic fatty acid with the second carboxyl at the end of the alkyl chain in the omega-position (alpha,omega-tetradecyldicarboxylic acid) stimulated respiration of the mitochondria at a significantly higher concentration than myristic acid with the same number of carbon atoms, but unlike the latter nearly failed to decrease the transmembrane potential DeltaPsi. Neither carboxyatractylate nor glutamate inhibited the respiration stimulated by this dicarboxylic fatty acid.

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KEY WORDS: uncoupling, dicarboxylic fatty acid, glutamate, carboxyatractylate, aspartate/glutamate antiporter, ADP/ATP-antiporter, liver mitochondria

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