Involvement of phosphate carrier as a part of complex with ADP/ATP and aspartate/glutamate antiporters in palmitic acid-induced uncoupling in liver mitochondria |
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Authors: | V N Samartsev O V Kozhina E I Marchik L V Shamagulova |
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Institution: | 1.Mari State University,Yoshkar-Ola,Russia |
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Abstract: | In liver mitochondria, the phosphate carrier is involved in protonophoric uncoupling effect of fatty acids together with ADP/ATP
and aspartate/glutamate antiporters (Samartsev et al. 2003. Biochemistry (Moscow). 68, 618–629). Liver mitochondria depleted of endogenous oxidation substrates (exhausted mitochondria) have been used in the
present work. In these mitochondria, like in the intact liver mitochondria, the specific inhibitor of ADP/ATP antiporter (carboxyatractylate)
and the substrate of aspartate/glutamate antiporter (aspartate) suppress the uncoupling activity of palmitic acid. It is shown
that in exhausted mitochondria the substrate of phosphate carrier (inorganic phosphate) and its nonspecific inhibitor mersalyl
partially suppress palmitic acid-induced uncoupling due to decrease in the component of uncoupling activity sensitive to carboxyatractylate
and aspartate. In the presence of inorganic phosphate or mersalyl, carboxyatractylate and aspartate added separately subsequent
to palmitic acid do not suppress its uncoupling activity. They are effective only when added jointly. In the presence of thiourea
or pyruvate, such effects of inorganic phosphate and mersalyl are not observed. It is supposed that in the presence of inorganic
phosphate or mersalyl and under the condition of oxidation of critical SH-groups in mitochondria, the phosphate carrier, ADP/ATP
antiporter, and aspartate/glutamate antiporter are involved in uncoupling function together with the general fatty acid pool
as an uncoupling complex. The role of phosphate carrier in this complex may consist in facilitation of lateral transfer of
the fatty acid molecules from one antiporter to another. |
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