title: The role of autophagy in alpha-1-antitrypsin deficiency.
abstract: In the classical form of alpha-1-antitrypsin (AT) deficiency, a mutant protein accumulates in the endoplasmic reticulum of liver cells, causing hepatic fibrosis and hepatocellular carcinoma by a gain-of-toxic function mechanism. Autophagy is specifically activated by the accumulation of mutant AT, and the autophagy plays a key role in intracellular degradation of this mutant protein. Our recent study indicates that an autophagy enhancer drug can decrease the hepatic load of mutant AT and reduce hepatic fibrosis in a mouse model of AT deficiency. In this chapter, we discuss what is known about autophagy in AT deficiency and methods for characterizing autophagy in cell lines and animal models.
authors.affiliation: Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA.
authors.forename: Tunda
authors.initials: T
authors.lastname: Hidvegi
authors.forename: Amitava
authors.initials: A
authors.lastname: Mukherjee
authors.forename: Michael
authors.initials: M
authors.lastname: Ewing
authors.forename: Carolyn
authors.initials: C
authors.lastname: Kemp
authors.forename: David H
authors.initials: DH
authors.lastname: Perlmutter
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D004586:Electrophoresis; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D016253:Microscopy, Immunoelectron; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000515:alpha 1-Antitrypsin