Apoptosis is a primary characteristic in the pathogenesis of liver disease. Hepatic apoptosis is regulated by autophagic activity. However, mechanisms mediating their interaction remain to be determined. Basal level of autophagy ensures the physiological turnover of old and damaged organelles. Autophagy also is an adaptive response under stressful conditions. Autophagy can control cell fate through different cross-talk signals. A complex interplay between hepatic autophagy and apoptosis determines the degree of hepatic apoptosis and the progression of liver disease as demonstrated by pre-clinical models and clinical trials. This review summarizes recent advances on roles of autophagy that plays in pathophysiology of liver. The autophagic pathway can be a novel therapeutic target for liver disease.
Keywords: ALT, alanine aminotransferase; AMBRA-1, activating molecule in Beclin-1-regulated autophagy; APAP, N-acetyl-p-aminophenol; ATP, adenosine triphosphate; Atg, autophagy-related gene; BH3, Bcl-2 homology domain-3; BNIP, Bcl-2/adenovirus E1B 19 kd-interacting protein; Barkor, Beclin-1-associated autophagy-related key regulator; Bcl-2, B-cell lymphoma-2; Bcl-xL, B-cell lymphoma extra long; Beclin-1, Bcl-2-interacting protein-1; CSE, cigarette smoke extract; DISC, death-inducing signaling complex; DNA, DNA; DRAM, damage regulated autophagic modulator; Drp1, dynamin-related protein 1; ER stress, endoplasmic reticulum stress; FADD, Fas-associated protein with death domain; FFA, free fatty acids; HBV, hepatitis B virus; HBx, hepatitis B X protein; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HSC, hepatic stellate cells; LAMP-2, lysosome-associated membrane protein 2; LD, lipid droplets; MDBs, Mallory-Denk bodies; MOMP, mitochondrial outer membrane permiabilization; Microtubule LC3, microtubule light chain 3; PCD, programmed cell death; PI3KC3, phosphatidylinositol-3-kinase class-3; RNA, ribonucleic acid; ROS, reactive oxygen species; TNFα, tumor necrosis factor-α; TUNEL, terminal deoxynucleotidyl transferase dUTP nick-end labeling; UVRAG, UV-resistance-associated gene; Vps34, vacuolar protein sorting-34; apoptosis; autophagy; c-FLIP, cellular FLICE-like inhibitor protein; cross-talk; liver injury; mTOR, mammalian target of rapamycin; mechanism; siRNA, small interfering RNA.