title: 3,5-diiodo-L-thyronine upregulates rat-liver mitochondrial F(o)F(1)-ATP synthase by GA-binding protein/nuclear respiratory factor-2.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry, Physics and Biology, University of Bari, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mangiullo
authors.forename: Antonio
authors.initials: A
authors.lastname: Gnoni
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Damiano
authors.forename: Luisa
authors.initials: L
authors.lastname: Siculella
authors.forename: Franco
authors.initials: F
authors.lastname: Zanotti
authors.forename: Sergio
authors.initials: S
authors.lastname: Papa
authors.forename: Gabriele V
authors.initials: GV
authors.lastname: Gnoni
mesh_terms: 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
chemical_list: D004104:Diiodothyronines; D051268:GA-Binding Protein Transcription Factor; D012333:RNA, Messenger; C030103:3,5-diiodothyronine; D025261:Mitochondrial Proton-Translocating ATPases