Hypothyroid state and membrane fatty acid composition influence cardiac mitochondrial pyruvate oxidation.

Pyruvate oxidation was measured in cardiac mitochondria from euthyroid and hypothyroid rats fed diets enriched with either omega-6 or omega-3 fatty acids. Both State 4 and State 3 rates of pyruvate-dependent respiration were markedly reduced in hypothyroid mitochondria, regardless of diet consumed, compared to euthyroid controls. Respiratory control ratios and ADP/O ratios were the same under all treatments. While there was no significant effect of diet on respiration in euthyroid mitochondria, pyruvate oxidation was 28% higher in hypothyroid mitochondria from animals fed the omega-3 diet compared to those fed the omega-6 diet. Depressed respiration in the hypothyroid state was correlated with 18% more phosphatidylcholine in the inner mitochondrial membrane whereas phosphatidylethanolamine was 17% lower and cardiolipin 32% lower compared to controls. The total phospholipid fatty acid composition was not affected by the hypothyroid state. However, enhanced respiration in hypothyroid animals fed the omega-3 diet was associated with a 3-fold increase in monounsaturated fatty acids in the cardiolipin fraction, and a 12-fold increase in omega-3 fatty acids, primarily 22:5(omega-3) and 22:6(omega-3). The data suggest that membrane levels of cardiolipin and its omega-3 fatty acid content modulate pyruvate transport in hypothyroid mitochondria.