Effect of 3,5-di-iodo-L-thyronine on the Mitochondrial Energy-Transduction Apparatus

Biochem J. 1998 Feb 15;330 ( Pt 1)(Pt 1):521-6. doi: 10.1042/bj3300521.

Abstract

We examined the effect of a single injection of 3,5-di-iodo-L-thyronine (3,5-T2) (150 microg/100 g body weight) on the rat liver mitochondrial energy-transduction apparatus. We applied 'top-down' elasticity analysis, 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 mitochondrial inner-membrane potential (DeltaPsi; 'substrate oxidation') and those 'consuming' it ('proton leak' and 'phosphorylating system'). The results show that 1 h after the injection of 3,5-T2, state 4 (respiratory 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 significantly increased (by approx. 30%). 'Top-down' elasticity analysis revealed that these increases were due to the stimulation of reactions involved in substrate oxidation; neither 'proton leak' nor the 'phosphorylating system' was influenced by 3,5-T2. Using the same approach we divided the respiratory chain into two blocks of reactions: cytochrome c reducers and cytochrome c oxidizers. We found that both cytochrome c reducers and cytochrome c oxidizers are targets for 3,5-T2. The rapidity with which 3,5-T2 acts in stimulating the mitochondrial respiration rate suggests to us that di-iodo-L-thyronine may play an important role in the physiological conditions in which rapid energy utilization is required, such as cold exposure or overfeeding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytochrome c Group / metabolism
  • Diiodothyronines / pharmacology*
  • Energy Metabolism / drug effects
  • Hydrogen-Ion Concentration
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / metabolism
  • Oxidation-Reduction
  • Oxidative Phosphorylation / drug effects
  • Oxygen Consumption / drug effects
  • Rats
  • Rats, Wistar

Substances

  • Cytochrome c Group
  • Diiodothyronines
  • 3,5-diiodothyronine