Impaired TFEB-Mediated Lysosome Biogenesis and Autophagy Promote Chronic Ethanol-Induced Liver Injury and Steatosis in Mice

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 155; no. 3; pp. 865 - 879.e12
• Main Authors: Chao, Xiaojuan, Wang, Shaogui, Zhao, Katrina, Li, Yuan, Williams, Jessica A., Li, Tiangang, Chavan, Hemantkumar, Krishnamurthy, Partha, He, Xi C., Li, Linheng, Ballabio, Andrea, Ni, Hong-Min, Ding, Wen-Xing
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2018
• Subjects: Animals; Autophagy - genetics; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - physiology; Ethanol; Fatty Liver; Fatty Liver - genetics; Gene Regulation; Hepatic Protection; Hepatocytes - physiology; Liver - metabolism; Liver Diseases, Alcoholic - genetics; Lysosomes - physiology; Mice; Mice, Knockout; Mouse Model; Organelle Biogenesis; TOR Serine-Threonine Kinases - physiology; GTP; Ad; PGC1α; ALT; EtOH; Gene Regulation; GFP; ATP6V1H; ATP6V1D; LC3; Ly6B; WT; Mouse Model; ATP6V0E1; KO; Lamp1; H&E; AH; TFE3; TFEB; DKO; TSC1; Ctrl; EGTA; PKCβ; Fatty Liver; Hepatic Protection; ERK1/2; TG; Tor; ALD; LDs; Leu; mTORC1

Defects in lysosome function and autophagy contribute to the pathogenesis of alcoholic liver disease. We investigated the mechanisms by which alcohol consumption affects these processes by evaluating the functions of transcription factor EB (TFEB), which regulates lysosomal biogenesis. We performed...