Journal
CELL CYCLE
Volume 14, Issue 11, Pages 1631-1642Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2015.1038685
Keywords
apoptosis; liver injury; mechanism; cross-talk; autophagy; LAMP-2, lysosome-associated membrane protein 2; Vps34, vacuolar protein sorting-34; ER stress, endoplasmic reticulum stress; BH3, Bcl-2 homology domain-3; FADD, Fas-associated protein with death domain; Bcl-x(L), B-cell lymphoma extra long; CSE, cigarette smoke extract; LD, lipid droplets; HBV, hepatitis B virus; HSC, hepatic stellate cells; Beclin-1, Bcl-2-interacting protein-1; HBx, hepatitis B X protein; PI3KC3, phosphatidylinositol-3-kinase class-3; HCV, hepatitis C virus; FFA, free fatty acids; ALT, alanine aminotransferase; PCD, programmed cell death; DNA, DNA; Atg, autophagy-related gene; c-FLIP, cellular FLICE-like inhibitor protein; RNA, ribonucleic acid; BNIP, Bcl-2/adenovirus E1B 19 k(d)-interacting protein; MDBs, Mallory-Denk bodies; AMBRA-1, activating molecule in Beclin-1-regulated autophagy; APAP, N-acetyl-p-aminophenol; Drp1, dynamin-related protein 1; Microtubule LC3, microtubule light chain 3; HCC, hepatocellular carcinoma; ATP, adenosine triphosphate; DISC, death-inducing signaling complex; ROS, reactive oxygen species; DRAM, damage regulated autophagic modulator; TNF alpha, tumor necrosis factor-alpha; UVRAG, UV-resistance-associated gene; Bcl-2, B-cell lymphoma-2; siRNA, small interfering RNA; mTOR, mammalian target of rapamycin; Barkor, Beclin-1-associated autophagy-related key regulator; MOMP, mitochondrial outer membrane permiabilization; TUNEL, terminal deoxynucleotidyl transferase dUTP nick-end labeling
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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.
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