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

The thyroid hormone, T 3, 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. T 3 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 T 3. T 3 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, T 3 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 T 3-activated autophagy and lipolysis. Moreover, treatment with autolysosome maturation inhibitors, ammonium chloride and chloroquine, not only suppressed the T 3-activated autophagic process but also lipid metabolism. Our results collectively suggested that T 3 regulates lipid metabolism through a C19orf80-activated autophagic process.