3,5-diiodo-L-thyronine upregulates rat-liver mitochondrial F0F1-ATP synthase by GA-binding protein/nuclear respiratory factor-2

作者：Mangiullo Roberto; Gnoni Antonio; Damiano Fabrizio; Siculella Luisa; Zanotti Franco; Papa Sergio; Gnoni Gabriele V^*

来源：Biochimica et Biophysica Acta-Bioenergetics, 2010, 1797(2): 233-240.

DOI：10.1016/j.bbabio.2009.10.009

• 3,5-diiodothyronine
• F0F1-ATP synthase
• Nuclear respiratory factor-2
• Oxidative phosphorylation
• Rat-liver mitochondria

Besides triiodothyronine (T-3), 3,5-diiodo-L-thyronine (T-2) has been reported to affect mitochondrial bioenergetic parameters. T-2 effects have been considered as independent of protein synthesis. Here. we investigated the effect of in vivo chronic T-2 administration to hypothyroid rats on liver mitochondrial F0F1-ATP synthase activity and expression. T-2 increased state 4 and state 3 oxygen consumption and raised ATP synthesis and hydrolysis, which were reduced in hypothyroid rats. Immunoblotting analysis showed that T-2 up-regulated the expression of several subunits (alpha, beta, F0I-PVP and OSCP) of the ATP synthase. The observed increase of p-subunit mRNA accumulation suggested a T-2-mediated nuclear effect. Then, the molecular basis underlying T-2 effects was investigated. Our results support the notion that the beta-subunit of ATP synthase is indirectly regulated by T-2 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 T-2 role on bioenergetic mechanisms.

• 出版日期2010-2