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Thyroid Hormone Stimulation of Autophagy Is Essential for Mitochondrial Biogenesis and Activity in Skeletal Muscle.

Publication ,  Journal Article
Lesmana, R; Sinha, RA; Singh, BK; Zhou, J; Ohba, K; Wu, Y; Yau, WWY; Bay, B-H; Yen, PM
Published in: Endocrinology
January 2016

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 Autophagy-related gene (Atg)5 short hairpin RNA (shRNA). Induction of ROS and 5'adenosine monophosphate-activated 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.

Duke Scholars

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Published In

Endocrinology

DOI

EISSN

1945-7170

Publication Date

January 2016

Volume

157

Issue

1

Start / End Page

23 / 38

Location

United States

Related Subject Headings

  • Triiodothyronine
  • Transcription Factors
  • Thyroxine
  • TOR Serine-Threonine Kinases
  • Signal Transduction
  • Reactive Oxygen Species
  • RNA Interference
  • Protein Serine-Threonine Kinases
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Oxygen Consumption
 

Citation

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Chicago
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Lesmana, R., Sinha, R. A., Singh, B. K., Zhou, J., Ohba, K., Wu, Y., … Yen, P. M. (2016). Thyroid Hormone Stimulation of Autophagy Is Essential for Mitochondrial Biogenesis and Activity in Skeletal Muscle. Endocrinology, 157(1), 23–38. https://doi.org/10.1210/en.2015-1632
Lesmana, Ronny, Rohit A. Sinha, Brijesh K. Singh, Jin Zhou, Kenji Ohba, Yajun Wu, Winifred W. Y. Yau, Boon-Huat Bay, and Paul M. Yen. “Thyroid Hormone Stimulation of Autophagy Is Essential for Mitochondrial Biogenesis and Activity in Skeletal Muscle.Endocrinology 157, no. 1 (January 2016): 23–38. https://doi.org/10.1210/en.2015-1632.
Lesmana R, Sinha RA, Singh BK, Zhou J, Ohba K, Wu Y, et al. Thyroid Hormone Stimulation of Autophagy Is Essential for Mitochondrial Biogenesis and Activity in Skeletal Muscle. Endocrinology. 2016 Jan;157(1):23–38.
Lesmana, Ronny, et al. “Thyroid Hormone Stimulation of Autophagy Is Essential for Mitochondrial Biogenesis and Activity in Skeletal Muscle.Endocrinology, vol. 157, no. 1, Jan. 2016, pp. 23–38. Pubmed, doi:10.1210/en.2015-1632.
Lesmana R, Sinha RA, Singh BK, Zhou J, Ohba K, Wu Y, Yau WWY, Bay B-H, Yen PM. Thyroid Hormone Stimulation of Autophagy Is Essential for Mitochondrial Biogenesis and Activity in Skeletal Muscle. Endocrinology. 2016 Jan;157(1):23–38.
Journal cover image

Published In

Endocrinology

DOI

EISSN

1945-7170

Publication Date

January 2016

Volume

157

Issue

1

Start / End Page

23 / 38

Location

United States

Related Subject Headings

  • Triiodothyronine
  • Transcription Factors
  • Thyroxine
  • TOR Serine-Threonine Kinases
  • Signal Transduction
  • Reactive Oxygen Species
  • RNA Interference
  • Protein Serine-Threonine Kinases
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Oxygen Consumption