3,5-diiodo-L-thyronine upregulates rat-liver mitochondrial F(o)F(1)-ATP synthase by GA-binding protein/nuclear respiratory factor-2.
Besides triiodothyronine (T3), 3,5-diiodo-L-thyronine (T2) has been reported to affect mitochondrial bioenergetic parameters. T2 effects have been considered as independent of protein synthesis. Here, we investigated the effect of in vivo chronic T2 administration to hypothyroid rats on liver mitochondrial F(o)F(1)-ATP synthase activity and expression. T2 increased state 4 and state 3 oxygen consumption and raised ATP synthesis and hydrolysis, which were reduced in hypothyroid rats. Immunoblotting analysis showed that T2 up-regulated the expression of several subunits (alpha, beta, F(o)I-PVP and OSCP) of the ATP synthase. The observed increase of beta-subunit mRNA accumulation suggested a T2-mediated nuclear effect. Then, the molecular basis underlying T2 effects was investigated. Our results support the notion that the beta-subunit of ATP synthase is indirectly regulated by T2 through, at least in part, the activation of the transcription factor GA-binding protein/nuclear respiratory factor-2. These findings provide new insights into the T2 role on bioenergetic mechanisms.
Mangiullo
Roberto
R
Department of Medical Biochemistry, Physics and Biology, University of Bari, Italy.
Gnoni
Antonio
A
Damiano
Fabrizio
F
Siculella
Luisa
L
Zanotti
Franco
F
Papa
Sergio
S
Gnoni
Gabriele V
GV
D000818:Animals; D047369:Chromatin Immunoprecipitation; D004104:Diiodothyronines / Q000494:pharmacology*; D051268:GA-Binding Protein Transcription Factor / Q000235:genetics / Q000378:metabolism*; D007037:Hypothyroidism / Q000188:drug therapy / Q000378:metabolism*; D015151:Immunoblotting; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D010101:Oxygen Consumption; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004104:Diiodothyronines; D051268:GA-Binding Protein Transcription Factor; D012333:RNA, Messenger; C030103:3,5-diiodothyronine; D025261:Mitochondrial Proton-Translocating ATPases