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Ethanol-triggered Lipophagy Requires SQSTM1 in AML12 Hepatic Cells. 2017

Lin Wang, and Jun Zhou, and Shengmin Yan, and Guangsheng Lei, and Chao-Hung Lee, and Xiao-Ming Yin
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

Ethanol-induced hepatic lipophagy plays an important cytoprotective role against liver injury, but its mechanism is not fully determined. In the present study, ethanol-induced lipophagy was studied in an immortalized mouse hepatocyte line, AML12. We found that ethanol treatment elevated lipid content in these cells, which could be regulated by autophagy. To determine the potential mechanism, we investigated the role of a key adaptor molecule SQSTM1/p62. SQSTM1 can bind to LC3 on autophagosomes and ubiquitinated molecules on cargos, thus facilitating the autophagic engulfment of the cargo. We found that both LC3 and SQSTM1 could colocalize with lipid droplets (LDs) following ethanol treatment. Colocalization of LC3 with LDs was significantly inhibited by SQSTM1 knockdown, which also reduced ethanol-induced lipid elevation. In addition, increased ubiquitin signals were found to colocalize with SQSTM1 on LDs in response to ethanol. Moreover, the SQSTM1 signal was colocalized with that of perilipin1, a major protein on LDs. Finally, perilipin1 knockdown significantly altered ethanol-induced lipophagy. Taken together, these data support a model in which autophagosomes were directed to the LDs via SQSTM1, which bound to ubiquitinated proteins, possibly including perilipin 1, on LDs. This study provides a potential mechanistic explanation to how ethanol induces lipophagy in hepatocytes.

UI MeSH Term Description Entries
D008055 Lipids A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed) Lipid
D008869 Microtubule-Associated Proteins High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules. Ensconsin,Epithelial MAP, 115 kDa,Epithelial Microtubule-Associate Protein, 115 kDa,MAP4,Microtubule Associated Protein,Microtubule Associated Protein 4,Microtubule Associated Protein 7,Microtubule-Associated Protein,Microtubule-Associated Protein 7,E-MAP-115,MAP1 Microtubule-Associated Protein,MAP2 Microtubule-Associated Protein,MAP3 Microtubule-Associated Protein,Microtubule Associated Proteins,Microtubule-Associated Protein 1,Microtubule-Associated Protein 2,Microtubule-Associated Protein 3,7, Microtubule-Associated Protein,Associated Protein, Microtubule,E MAP 115,Epithelial Microtubule Associate Protein, 115 kDa,MAP1 Microtubule Associated Protein,MAP2 Microtubule Associated Protein,MAP3 Microtubule Associated Protein,Microtubule Associated Protein 1,Microtubule Associated Protein 2,Microtubule Associated Protein 3,Microtubule-Associated Protein, MAP1,Microtubule-Associated Protein, MAP2,Microtubule-Associated Protein, MAP3,Protein 7, Microtubule-Associated,Protein, Microtubule Associated,Protein, Microtubule-Associated
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D000070778 Perilipin-1 A lipid droplet protein that is expressed primarily by ADIPOCYTES of WHITE ADIPOSE TISSUE and BROWN ADIPOSE TISSUE. It co-localizes with MACROPHAGES and FOAM CELLS of artherosclerotic lesions and stabilizes LIPID DROPLETS by inhibiting HORMONE SENSITIVE LIPASE. It may also protect TRIGLYCERIDES against hydrolysis within the PLASMA MEMBRANE and modulate CHOLESTEROL ESTER HYDROLASE activity. PERI Protein,Perilipin,Perilipin A Protein,Perilipin B Protein,Perilipin Protein,Plin Protein,Perilipin 1,Protein, PERI,Protein, Perilipin,Protein, Perilipin A,Protein, Perilipin B,Protein, Plin
D000071182 Autophagosomes Large spherical double-layered structures which function in AUTOPHAGY to engulf intracellular components such as ORGANELLES or pathogens. Their outer membrane then fuses with the LYSOSOME (forming the AUTOLYSOSOME) and the inner membrane and contents are digested by lysosomal HYDROLASES. Phagophores,Autophagosome,Phagophore
D000071456 Sequestosome-1 Protein A multidomain protein that is highly conserved among multicellular organisms. It contains a ZZ-type ZINC FINGER domain, C-terminal UBIQUITIN - associated (UBA) domain, and interacts with many other signaling proteins and enzymes including, atypical PROTEIN KINASE C; TNF RECEPTOR-ASSOCIATED FACTOR 6; subunits of the mTORC1 complex, and CASPASE-8. It functions in AUTOPHAGY as a receptor for the degradation of ubiquitinated substrates, and to co-ordinate signaling in response to OXIDATIVE STRESS. EBI3-Associated Protein of 60 KDa,EBIAP Protein,Phosphotyrosine-Independent Ligand For The Lck SH2 Domain Of 62 Kda,Ubiquitin-Binding Protein p62,EBI3 Associated Protein of 60 KDa,Phosphotyrosine Independent Ligand For The Lck SH2 Domain Of 62 Kda,Sequestosome 1 Protein,Ubiquitin Binding Protein p62
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001343 Autophagy The segregation and degradation of various cytoplasmic constituents via engulfment by MULTIVESICULAR BODIES; VACUOLES; or AUTOPHAGOSOMES and their digestion by LYSOSOMES. It plays an important role in BIOLOGICAL METAMORPHOSIS and in the removal of bone by OSTEOCLASTS. Defective autophagy is associated with various diseases, including NEURODEGENERATIVE DISEASES and cancer. Autophagocytosis,ER-Phagy,Lipophagy,Nucleophagy,Reticulophagy,Ribophagy,Autophagy, Cellular,Cellular Autophagy,ER Phagy
D050356 Lipid Metabolism Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS. Metabolism, Lipid

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