The purpose of this study was to investigate the effects of thyroid state on rates and sites of H(2)O(2) production in rat muscle mitochondria. With Complex I- and Complex II-linked substrates, hypothyroidism decreased and hyperthyroidism increased the rates of O(2) consumption during State 4 and State 3 respiration and the rates of H(2)O(2) release during State 4 respiration. During State 3, the rates of H(2)O(2) release were not affected by thyroid state. However, the mitochondrial capacity to remove H(2)O(2) increased in the transition from hypothyroid to hyperthyroid state, thus suggesting that an increase in H(2)O(2) production rate also occurred in such a transition during State 3 respiration. The observation that mitochondrial coenzyme Q levels and cytochrome oxidase activities are higher in the hyperthyroid and lower in the hypothyroid groups suggests that the modifications of H(2)O(2) production are due to a modulation by thyroid hormone of the mitochondrial content of autoxidizable electron carriers. This idea is supported by measurements of H(2)O(2) release in the presence of respiratory inhibitors. In fact, such measurements indicate that the thyroid state-linked changes in H(2)O(2) production occur at both generator sites of the respiratory chain.
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