Chromosome 19 open reading frame 80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism

Yi Hsin Tseng, Po Yuan Ke, Chia Jung Liao, Sheng Ming Wu, Hsiang Cheng Chi, Chung Ying Tsai, Cheng Yi Chen, Yang Hsiang Lin, Kwang Huei Lin

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42 Citations (Scopus)

Abstract

The thyroid hormone, T3, regulates cell growth, differentiation and development through binding to the nuclear thyroid hormone receptor (THR), a member of the steroid/TR superfamily of ligand-dependent transcriptional factors. T3 modulates lipid metabolism in liver, although the detailed molecular mechanisms are unclear at present. Here, by a microarray analysis, we identified a novel chromosome 19 open reading frame 80 (C19orf80) which was activated by T3. T3 stimulation led to upregulation of both mRNA and protein levels of C19orf80. Immunofluorescence analysis revealed a vesicle-like pattern of C19orf80 around lipid droplets or within the lysosome-associated compartment in cells. Furthermore, T3 treatment as well as C19orf80 overexpression specifically activated the autophagic response and lipid metabolism, as observed from lipidated LC3 (LC3-II) and levels of oxygen consumption rate, respectively. Reciprocally, knockdown of C19orf80 obstructed T3-activated autophagy and lipolysis. Moreover, treatment with autolysosome maturation inhibitors, ammonium chloride and chloroquine, not only suppressed the T3-activated autophagic process but also lipid metabolism. Our results collectively suggested that T3 regulates lipid metabolism through a C19orf80- activated autophagic process.

Original languageEnglish
Pages (from-to)20-31
Number of pages12
JournalAutophagy
Volume10
Issue number1
DOIs
Publication statusPublished - 2014 Jan

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Tseng, Y. H., Ke, P. Y., Liao, C. J., Wu, S. M., Chi, H. C., Tsai, C. Y., Chen, C. Y., Lin, Y. H., & Lin, K. H. (2014). Chromosome 19 open reading frame 80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism. Autophagy, 10(1), 20-31. https://doi.org/10.4161/auto.26126