Effects of the novel thyroid hormone analogues, SKF L-94901, DIBIT, and 3'-AC-T2 on mitochondrial function.

The effects of L-T3 (3,3',5-triiodo-L-thyronine) and three novel analogues, SKF L-94901 (3,5-Dibromo-3'-pyridazinone-L-thyronine), Dibit (3,5-Dibromo-3'-isopropyl-L-thyronine), and 3'-Ac-T2(3'-Acetyl-3,5,-Diiodo-L-thyronine), on mitochondrial parameters were determined in hypothyroid rats. The parameters include the 24 hour hormone-induced changes in the bc1 complex and in the proton permeability of the mitochondrial inner membrane. The cardiac sparing analogue, SKF L-94901, had no effect on mitochondrial respiration or proton permeability; but the analogue did increase a-glycerophosphate dehydrogenase activity, mitochondrial ubiquinone content, and altered the bypass respiration in the bc1 complex.

Effects of 3,3',5-triiodo-L-thyronine (L-T3) and T3 analogues on mitochondrial function.

The effects of L-T3 and several analogues on mitochondrial parameters were determined in hypothyroid rats. These parameters include the 24 hour hormone-induced changes in the bc1 complex and in the inner membrane's proton permeability. L-T3, and all analogues except rT3, increased mitochondrial ubiquinone to euthyroid levels.

The early triiodothyronine-induced changes in state IV respiration is not regulated by the proton permeability of the mitochondrial inner membrane.

The time course of changes in mitochondrial respiration, alpha-glycerophosphate dehydrogenase activity, and inner membrane proton permeability and the effects of protein synthesis inhibition was determined in hypothyroid rats treated with triiodothyronine. Respiratory rates, alpha-glycerophosphate dehydrogenase activity and proton permeability were decreased in hypothyroid rats and rose to euthyroid levels 9-12 hours after triiodothyronine treatment. Some rats received actinomycin D with the hormone to inhibit protein synthesis.

Effects of thyroid hormones on the bypasses of the antimycin A block in the bc1 complex of rat liver mitochondria.

The effect of thyroid hormones on the electron flow through the bc1 complex of rat liver mitochondria was studied using two dye bypasses of the Antimycin A block of the bc1 complex by the method of Alexandre and Lehninger (Biochim. Biophys. Acta 767:120; 1984).

Thyroid hormone effects on the State IV proton motive force in rat liver mitochondria.

In order to further investigate the mechanisms regulating the control of mitochondrial respiration by thyroid hormone, the proton motive force was measured during State IV respiration in liver mitochondria isolated from euthyroid, hyperthyroid, hypothyroid and T3-treated hypothyroid rats. The proton motive force was significantly higher in the hyperthyroid group due to an increased delta pH. The proton motive force of hypothyroid mitochondria was lower than controls due to a decreased membrane potential.