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Title: Thyroid hormone stimulation of autophagy is essential for mitochondrial biogenesis and activity in skeletal muscle
Authors: Lesmana R., Sinha R.A. 
Singh B.K. 
Zhou J. 
Ohba K.
Wu Y. 
Yau W.W. 
Bay B.-H. 
Yen P.M. 
Issue Date: 2016
Publisher: Endocrine Society
Citation: Lesmana R., Sinha R.A., Singh B.K., Zhou J., Ohba K., Wu Y., Yau W.W., Bay B.-H., Yen P.M. (2016). Thyroid hormone stimulation of autophagy is essential for mitochondrial biogenesis and activity in skeletal muscle. Endocrinology 157 (1) : 23-38. ScholarBank@NUS Repository.
Abstract: Thyroid hormone (TH) and autophagy share similar functions in regulating skeletal muscle growth, regeneration, and differentiation. Although TH recently has been shown to increase autophagy in liver, the regulation and role of autophagy by this hormone in skeletal muscle is not known. Here, using both in vitro and in vivo models, we demonstrated that TH induces autophagy in a dose- and time-dependent manner in skeletal muscle. TH induction of autophagy involved reactive oxygen species (ROS) stimulation of 5'adenosine monophosphate-activated protein kinase (AMPK)-Mammalian target of rapamycin (mTOR)-Unc-51-like kinase 1 (Ulk1) signaling. TH also increased mRNA and protein expression of key autophagy genes, microtubule-associated protein light chain 3(LC3), Sequestosome 1(p62), and Ulk1, as well as genes that modulated autophagy and Forkhead box O (FOXO) 1/3a. TH increased mitochondrial protein synthesis and number as well as basal mitochondrial O2 consumption, ATP turnover, and maximal respiratory capacity. Surprisingly, mitochondrial activity and biogenesis were blunted when autophagy was blocked in muscle cells by Autophagyrelated gene (Atg)5 short hairpin RNA (shRNA). Induction of ROS and 5'adenosine monophosphateactivated protein kinase (AMPK) by TH played a significant role in the up-regulation of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A), the key regulator of mitochondrial synthesis. In summary, our findings showed that TH-mediated autophagy was essential for stimulation of mitochondrial biogenesis and activity in skeletal muscle. Moreover, autophagy and mitochondrial biogenesis were coupled in skeletal muscle via TH induction of mitochondrial activity and ROS generation. Copyright � 2016 by the Endocrine Society.
Source Title: Endocrinology
ISSN: 137227
DOI: 10.1210/en.2015-1632
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