NorUDCA promotes degradation of α1-antitrypsin mutant Z protein by inducing autophagy through AMPK/ULK1 pathway

• DOI: 10.1371/journal.pone.0200897
• Publication Date: 2018-08-01T13:36:53Z
• Authors: Youcai Tang; Keith S. Blomenkamp; Peter Fickert; Michael Trauner; Jeffrey H. Teckman
• Keywords: ATG16L1; ULK1; Protein Degradation

Alpha-1 Antitrypsin (α1AT) Deficiency is a genetic disease in which accumulation of α1AT mutant Z (α1ATZ) protein the ER hepatocytes causes chronic liver injury, fibrosis, and hepatocellular carcinoma. No effective medical therapy currently available for disease. We previously found that norUDCA improves deficiency associated by promoting autophagic degradation α1ATZ mouse model The current study unravels novel underlying cellular mechanism modulates autophagy. HTOZ cells, modified from HeLa Tet-Off cells transfection with resulting pTRE1-ATZ plasmid expressing proteins, were studied these experiments. role inducing autophagy, autophagy-mediated AMPK norUDCA-induced autophagy examined report. NorUDCA promoted disposal via cells. Activation was required degradation. Moreover, mTOR/ULK1 involved activation Our results provide mechanistic insights into therapeutic action clearance vitro suggest approach treatment its diseases.