Autophagy in liver diseases.
Autophagy, or cellular self-digestion, is a cellular pathway crucial for development, differentiation, survival, and homeostasis. Its implication in human diseases has been highlighted during the last decade. Recent data show that autophagy is involved in major fields of hepatology. In liver ischemia reperfusion injury, autophagy mainly has a prosurvival activity allowing the cell for coping with nutrient starvation and anoxia. During hepatitis B or C infection, autophagy is also increased but subverted by viruses for their own benefit. In hepatocellular carcinoma, the autophagy level is decreased. In this context, autophagy has an anti-tumor role and therapeutic strategies increasing autophagy, as rapamycin, have a beneficial effect in patients. Moreover, in hepatocellular carcinoma, Beclin-1 level, an autophagy protein, has a prognostic significance. In α-1-antitrypsin deficiency, the aggregation-prone ATZ protein accumulates in the endoplasmic reticulum. This activates the autophagic response which aims at degrading mutant ATZ. Some FDA-approved drugs which enhance autophagy and the disposal of aggregation-prone proteins may be useful in α-1-antitrypsin deficiency. Following alcohol consumption, autophagy is decreased in liver cells, likely due to a decrease in intracellular 5'-AMP-activated protein kinase (AMPk) and due to an alteration in vesicle transport in hepatocytes. This decrease in autophagy contributes to the formation of Mallory-Denk bodies and to liver cell death. Hepatic autophagy is defective in the liver in obesity and its upregulation improves insulin sensitivity.
Rautou
Pierre-Emmanuel
PE
Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France. perautou@yahoo.fr
Mansouri
Abdellah
A
Lebrec
Didier
D
Durand
François
F
Valla
Dominique
D
Moreau
Richard
R
D055371:Acute Lung Injury / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000503:physiopathology; D005234:Fatty Liver / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006525:Hepatitis, Viral, Human / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D008107:Liver Diseases / Q000473:pathology* / Q000503:physiopathology*; D008108:Liver Diseases, Alcoholic / Q000473:pathology / Q000503:physiopathology; D008113:Liver Neoplasms / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008954:Models, Biological; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D019896:alpha 1-Antitrypsin Deficiency / Q000473:pathology / Q000503:physiopathology