title: Role of Protein Quality Control Failure in Alcoholic Hepatitis Pathogenesis.
abstract: The mechanisms of protein quality control in hepatocytes in cases of alcoholic hepatitis (AH) including ufmylation, FAT10ylation, metacaspase 1 (Mca1), ERAD (endoplasmic reticulum-associated degradation), JUNQ (juxta nuclear quality control), IPOD (insoluble protein deposit) autophagocytosis, and ER stress are reviewed. The Mallory-Denk body (MDB) formation develops in the hepatocytes in alcoholic hepatitis as a consequence of the failure of these protein quality control mechanisms to remove misfolded and damaged proteins and to prevent MDB aggresome formation within the cytoplasm of hepatocytes. The proteins involved in the quality control pathways are identified, quantitated, and visualized by immunofluorescent antibody staining of liver biopsies from patients with AH. Quantification of the proteins are achieved by measuring the fluorescent intensity using a morphometric system. Ufmylation and FAT10ylation pathways were downregulated, Mca1 pathways were upregulated, autophagocytosis was upregulated, and ER stress PERK (protein kinase RNA-like endoplasmic reticulum kinase) and CHOP (CCAAT/enhancer-binding protein homologous protein) mechanisms were upregulated.
  
  
  
  Despite the upregulation of several pathways of protein quality control, aggresomes (MDBs) still formed in the hepatocytes in AH. The pathogenesis of AH is due to the failure of protein quality control, which causes balloon-cell change with MDB formation and ER stress.
authors.affiliation: Harbor-UCLA Medical Center, Department of Pathology, Torrance, CA 90509, USA. sfrench@labiomed.org.|LA BioMed Research Institute, Torrance, CA 90502, USA. sfrench@labiomed.org.
authors.forename: Samuel W
authors.initials: SW
authors.lastname: French
authors.affiliation: Harbor-UCLA Medical Center, Department of Pathology, Torrance, CA 90509, USA. maryammasouminia@dhs.lacounty.gov.
authors.forename: Maryam
authors.initials: M
authors.lastname: Masouminia
authors.affiliation: LA BioMed Research Institute, Torrance, CA 90502, USA. Sara.smdz88@gmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Samadzadeh
authors.affiliation: LA BioMed Research Institute, Torrance, CA 90502, USA. brittanycaratillman@yahoo.com.
authors.forename: Brittany C
authors.initials: BC
authors.lastname: Tillman
authors.affiliation: Harbor-UCLA Medical Center, Department of Pathology, Torrance, CA 90509, USA. alejandromendoza@dhs.lacounty.gov.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Mendoza
authors.affiliation: LA BioMed Research Institute, Torrance, CA 90502, USA. bfrench@labiomed.org.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: French
mesh_terms: D000818:Animals; D001343:Autophagy; D059865:Endoplasmic Reticulum Stress; D006519:Hepatitis, Alcoholic / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D059748:Proteolysis
chemical_list: D011506:Proteins; D046988:Proteasome Endopeptidase Complex
keywords: CHOP; ER stress; FATylation; Mallory–Denk bodies; PERK; autophagocytosis; metacaspase 1; protein quality control; ufmylation