EFFECT OF 3,5-DI-IODO-L-THYRONINE ON THE MITOCHONDRIAL ENERGY-TRANSDUCTION APPARATUS

We examined the effect of a single injection of 3,5-di-iodo-L-thyronin e (3,5-T2) (150 mu g/100 g body weight) on the rat liver mitochondrial energy-transduction apparatus. We applied 'top-down' elasticity analy sis, which allows identification of the site of action of an effector within a metabolic pathway. This kinetic approach considers oxidative phosphorylation as two blocks of reactions: those generating the mitoc hondrial inner-membrane potential (Delta Psi; 'substrate oxidation') a nd those 'consuming' it ('proton leak' and 'phosphorylating system'); The results show that 1 h after the injection of 3,5-T2, state 4 (resp iratory state in which there is no ATP synthesis and the exogenous ADP added has been exhausted) and state 3 (respiratory state in which ATP synthesis is at maximal rate) of mitochondrial respiration were signi ficantly increased (by approx. 30 %). 'Top-down' elasticity analysis r evealed that these increases were due to the stimulation of reactions involved in substrate oxidation; neither 'proton leak' nor the 'phosph orylating system' was influenced by 3,5-T2. Using the same approach we divided the respiratory chain into two blocks of reactions: cytochrom e c reducers and cytochrome c oxidizers. We found that both cytochrome c reducers and cytochrome c oxidizers are targets for 3,5-T2. The rap idity with which 3,5-T2 acts in stimulating the mitochondrial respirat ion rate suggests to us that di-iodo-L-thyronine may play an important role in the physiological conditions in which rapid energy utilizatio n is required, such as cold exposure or overfeeding.