Wrutniak-Cabello Chantal, Casas François, Cabello Gérard
DMEM, Univ Montpellier, INRA, Montpellier, France.
Methods Mol Biol. 2018;1801:163-181. doi: 10.1007/978-1-4939-7902-8_14.
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 TRα1 mRNA encodes not only a nuclear thyroid hormone receptor but also two proteins imported into mitochondria 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 detecting two mitochondrial T3 binding proteins. In association with western blots using antibodies raised against the T3 nuclear receptor TRα1, mitochondrial T3 receptors were identified as truncated TRα1 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. In vitro experiments indicated that this T3 mitochondrial pathway affects cell differentiation, apoptosis, and transformation. Generation of transgenic mice demonstrated the involvement of this mitochondrial pathway in the determination of muscle phenotype, glucose metabolism, and thermogenesis.
甲状腺激素多种生理影响涉及多种途径这一可能性，引发了对T3核外受体存在情况的探索。目前，T3直接的线粒体途径已得到充分证实。TRα1 mRNA不仅编码一种核甲状腺激素受体，还编码两种导入线粒体的蛋白质，其分子量分别为43 kDa和28 kDa，这一发现为理解碘化激素的多效性影响提供了新线索。使用T3光亲和标记衍生物（T3-PAL）能够检测到两种线粒体T3结合蛋白。结合使用针对T3核受体TRα1产生的抗体进行的蛋白质印迹分析，线粒体T3受体被鉴定为截短的TRα1形式。在分离的线粒体中进行的导入和体外转录实验得出结论，p43是线粒体基因组的转录因子，可诱导线粒体/核相互作用的变化。体外实验表明，这种T3线粒体途径会影响细胞分化、凋亡和转化。转基因小鼠的产生证明了该线粒体途径参与肌肉表型的确定、葡萄糖代谢和产热过程。
