Intracellular Inclusions Containing Mutant α1-Antitrypsin Z Are Propagated in the Absence of Autophagic Activity

Abstract

Mutant α1-antitrypsin Z (α1-ATZ) protein, which has a tendency to form aggregated polymers as it accumulates within the endoplasmic reticulum of the liver cells, is associated with the development of chronic liver injury and hepatocellular carcinoma in hereditary α1-antitrypsin (α1-AT) deficiency. Previous studies have suggested that efficient intracellular degradation of α1-ATZ is correlated with protection from liver disease in and that the a the of α1-ATZ intracellular degradation has in the of deficiency. of the that is of the of the degradation of α1-ATZ and the of α1-ATZ cells, of the and α1-ATZ and of and a with of α1-ATZ to the that of α1-ATZ in the liver in is to that in the α1-ATZ and that degradation a in of Mutant α1-antitrypsin Z (α1-ATZ) protein, which has a tendency to form aggregated polymers as it accumulates within the endoplasmic reticulum of the liver cells, is associated with the development of chronic liver injury and hepatocellular carcinoma in hereditary α1-antitrypsin (α1-AT) deficiency. Previous studies have suggested that efficient intracellular degradation of α1-ATZ is correlated with protection from liver disease in and that the a the of α1-ATZ intracellular degradation has in the of deficiency. of the that is of the of the degradation of α1-ATZ and the of α1-ATZ cells, of the and α1-ATZ and of and a with of α1-ATZ to the that of α1-ATZ in the liver in is to that in the α1-ATZ and that degradation a in of α1-antitrypsin α1-antitrypsin endoplasmic α1-antitrypsin endoplasmic a is and liver is a of and the of the of in is to from and in and in is the of that the Z of is to in in the with of the α1-ATZ in the of liver the α1-ATZ of that of in the and to in is to a liver disease in is to a in which liver injury from the of of liver has to the that which to the of α1-ATZ a in which of liver disease and which from studies have that a in α1-ATZ with the of liver disease the which α1-ATZ is to in the liver disease of with of studies have the of the of in the and the of the 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