Acute administration of 3,5-diiodo-L-thyronine to hypothyroid rats affects bioenergetic parameters in rat skeletal muscle mitochondria

FEBS Lett. 2007 Dec 22;581(30):5911-6. doi: 10.1016/j.febslet.2007.11.073. Epub 2007 Dec 3.

Abstract

We investigated the mechanism by which 3,5-diiodo-l-thyronine (T2) affects skeletal muscle mitochondrial bioenergetic parameters following its acute administration to hypothyroid rats. One hour after injection, T2 increased both coupled and uncoupled respiration rates by +27% and +42%, respectively. Top-down elasticity analysis revealed that these effects were the result of increases in the substrate oxidation and mitochondrial uncoupling. Discriminating between proton-leak and redox-slip processes, we identified an increased mitochondrial proton conductance as the "pathway" underlying the effect of T2 on mitochondrial uncoupling. As a whole, these results may provide a mechanism by which T2 rapidly affects energy metabolism in hypothyroid rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / pharmacology
  • Cell Respiration / drug effects
  • Diiodothyronines / administration & dosage*
  • Diiodothyronines / pharmacology*
  • Energy Metabolism / drug effects*
  • Hypothyroidism / metabolism*
  • Kinetics
  • Male
  • Malonates / pharmacology
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria, Muscle / drug effects*
  • Mitochondria, Muscle / metabolism*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Oligomycins / pharmacology
  • Oxidation-Reduction / drug effects
  • Phosphorylation / drug effects
  • Protons
  • Rats
  • Rats, Wistar

Substances

  • Diiodothyronines
  • Malonates
  • Oligomycins
  • Protons
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
  • 3',5'-diiodothyronine
  • malonic acid