Goglia Fernando, Silvestri Elena, Lanni Antonia
Facoltà de Scienze, Università degli Studi del Sannio, Benevento, Italy.
Biosci Rep. 2002 Feb;22(1):17-32. doi: 10.1023/a:1016056905347.
Because of their central role in the regulation of energy-transduction, mitochondria, the major site of oxidative processes within the cell, are considered a likely subcellular target for the action that thyroid hormones exert on energy metabolism. However, the mechanism underlying the regulation of basal metabolic rate (BMR) by thyroid hormones still remains unclear. It has been suggested that these hormones might uncouple substrate oxidation from ATP synthesis, but there are no clear-cut data to support this idea. Two iodothyronines have been identified as effectors of the actions of thyroid hormones on energy metabolism: 3',3,5-triiodo-L-thyronine (T3) and 3,5-diiodo-L-thyronine (T2). Both have significant effects on BMR, but their mechanisms of action are not identical. T3 acts on the nucleus to influence the expression of genes involved in the regulation of cellular metabolism and mitochondria function; 3,5-T2, on the other hand, acts by directly influencing the mitochondrial energy-transduction apparatus. A molecular determinant of the effects of T3 could be uncoupling protein-3 (UCP-3), while the cytochrome-c oxidase complex is a possible target for 3,5-T2. In conclusion, it is likely that iodothyronines regulate energy metabolism by both short-term and long-term mechanisms, and that they act in more than one way in affecting mitochondrial functions.
由于线粒体在能量转导调节中发挥核心作用，而线粒体是细胞内氧化过程的主要场所，因此被认为是甲状腺激素作用于能量代谢的一个可能的亚细胞靶点。然而，甲状腺激素调节基础代谢率（BMR）的潜在机制仍不清楚。有人提出，这些激素可能使底物氧化与ATP合成解偶联，但尚无明确数据支持这一观点。已确定两种碘甲状腺原氨酸是甲状腺激素作用于能量代谢的效应物：3',3,5-三碘-L-甲状腺原氨酸（T3）和3,5-二碘-L-甲状腺原氨酸（T2）。两者对基础代谢率均有显著影响，但其作用机制并不相同。T3作用于细胞核，影响参与细胞代谢和线粒体功能调节的基因表达；另一方面，3,5-T2通过直接影响线粒体能量转导装置发挥作用。T3作用的一个分子决定因素可能是解偶联蛋白-3（UCP-3），而细胞色素c氧化酶复合体可能是3,5-T2的作用靶点。总之，碘甲状腺原氨酸很可能通过短期和长期机制调节能量代谢，并且它们在影响线粒体功能方面有多种作用方式。
