Acute administration of 3,5-diiodo-L-thyronine to hypothyroid rats affects bioenergetic parameters in rat skeletal muscle mitochondria.
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.
Dipartimento delle Scienze Biologiche, Sezione Fisiologia ed Igiene, Universitá degli Studi di Napoli Federico II, Via Mezzocannone, 8 80134 Napoli, Italy.
Assunta
A
Lombardi
Antonia
A
Lanni
Pieter
P
de Lange
Elena
E
Silvestri
Paola
P
Grasso
Rosalba
R
Senese
Fernando
F
Goglia
Maria
M
Moreno
D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D019069:Cell Respiration / Q000187:drug effects; D004104:Diiodothyronines / Q000008:administration & dosage* / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D007037:Hypothyroidism / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008314:Malonates / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011522:Protons; D051381:Rats; D017208:Rats, Wistar
D004104:Diiodothyronines; D008314:Malonates; D009840:Oligomycins; D011522:Protons; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; C030102:3',5'-diiodothyronine; C030290:malonic acid