{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:46:06Z","timestamp":1786977966869,"version":"build-2736575974"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T00:00:00Z","timestamp":1568246400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>\n                    Excessive accumulation of lipids in the liver is crucial in the pathogenesis of alcoholic steatohepatitis and may be partly mediated by impaired degradation of lipid droplets by autophagy. The E3 ubiquitin ligase SMAD\u2010specific E3 ubiquitin protein ligase 1 (SMURF1) regulates selective autophagy by ubiquitinating proteins on cargo destined for autophagic delivery to the lysosome for degradation. Here, we evaluated the role of SMURF1 in the regulation of hepatic lipid degradation in alcoholic steatohepatitis. In patients with severe alcoholic hepatitis, SMURF1 colocalized with lipid droplet membranes in liver explants. In a mouse model of alcoholic steatohepatitis,\n                    <jats:italic toggle=\"yes\">Smurf1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice fed an alcohol diet displayed increased hepatocyte accumulation of lipid droplets and triglycerides as well as more severe liver injury compared to wild\u2010type mice. The increased severity of liver steatosis in alcohol\u2010fed\n                    <jats:italic toggle=\"yes\">Smurf1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice was rescued by adeno\u2010associated virus (AAV) serotype 8\u2010mediated hepatic expression of wild\u2010type Smurf1 protein but not by mutant Smurf1 proteins either lacking the catalytically active cysteine 699 required for ubiquitin transfer or the N\u2010terminal C2 phospholipid membrane\u2010binding domain.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    Smurf1 plays a protective role in the pathogenesis of alcoholic steatohepatitis through a mechanism that requires both its ubiquitin\u2010ligase activity and C2 phospholipid\u2010binding domains. These findings have implications for understanding the roles of ubiquitin ligases in fatty liver disease.\n                  <\/jats:p>","DOI":"10.1002\/hep4.1427","type":"journal-article","created":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T08:39:06Z","timestamp":1568277546000},"page":"1450-1458","source":"Crossref","is-referenced-by-count":9,"title":["Protective Effect of SMAD\u2010Specific E3 Ubiquitin Protein Ligase 1 in Alcoholic Steatohepatitis in Mice"],"prefix":"10.1097","volume":"3","author":[{"given":"Jan","family":"Petrasek","sequence":"first","affiliation":[{"name":"Digestive and Liver Diseases Division and Center for Autophagy Research, Department of Internal Medicine,University of Texas Southwestern Medical Center,Dallas,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisa","family":"Erhartova","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Medicine,Prague,Czech 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