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Thyroid hormone action: The p43 mitochondrial pathway. Methods
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Edité par CCSD ; Humana Press -
The possibility that several pathways are involved in the multiplicity of thyroid hormone physiological influences led to searches for the occurrence of T3 extra nuclear receptors. The existence of a direct T3 mitochondrial _pathway is now well established. The demonstration that TR.al mRNA encodes not only a nuclear thyroid hormone receptor but also two proteins imported into ttùtochondria with molecular masses of 43 and 28 kDa has provided new clues to understand the pleiotropic influence of iodinated hormones. The use of a T3 photo affinity label derivative (T3-PAL) allowed detectiug two mitochondrial T3 binding proteins. In association with western blots using antibodies raised against the T3 nuclear receptor TRal, mitochondrial T3 receptors were identified as truncated T.Ral forms. Import and in organello transcription experiments performed in isolated mitochondria led to the conclusion that p43 is a transcription factor of the mitochondrial genome, inducing changes in the mitochondrial/nuclear crosstalk. Invitro experiments indicated that this T3 mitochondrial pathway affects cell differentiation, apoptosis, andtransformation. Generation of transgenic mice demonstrated the involve1nent of this mitochondrial pathwayin the determination of muscle phenotype, glucose metabolism, and thermogenesis.
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