{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T19:27:15Z","timestamp":1789932435910,"version":"4.0.1"},"reference-count":133,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and is closely associated with metabolic abnormalities. The causes of NAFLD are exceedingly complicated, and it is known that a variety of signaling pathways, endoplasmic reticulum stress, and mitochondrial dysfunction play a role in the pathogenesis of NAFLD. Recent studies have shown that ubiquitination and deubiquitination are involved in the regulation of the NAFLD pathophysiology. Protein ubiquitination is a dynamic and diverse post-translational alteration that affects various cellular biological processes. Numerous disorders, including NAFLD, exhibit imbalances in ubiquitination and deubiquitination. To highlight the significance of this post-translational modification in the pathogenesis of NAFLD and to aid in the development of new therapeutic approaches for the disease, we will discuss the role of enzymes involved in the processes of ubiquitination and deubiquitination, specifically E3 ubiquitin ligases and deubiquitinating enzymes that are important in the regulation of NAFLD.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1535362","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:10:27Z","timestamp":1744330227000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["The role of ubiquitination and deubiquitination in the pathogenesis of non-alcoholic fatty liver disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Lihui","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sutong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxiao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"15489","DOI":"10.3390\/ijms232415489","article-title":"Non-alcoholic fatty liver disease (NAFLD) pathogenesis and natural products for prevention and treatment","volume":"23","author":"Guo","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1097\/TP.0000000000002480","article-title":"Nonalcoholic fatty liver disease: basic pathogenetic mechanisms in the progression from NAFLD to NASH","volume":"103","author":"Pierantonelli","year":"2019","journal-title":"Transplantation"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.02.006","article-title":"NAFLD\/NASH","volume":"77","author":"Bugianesi","year":"2022","journal-title":"J Hepatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2022.08.011","article-title":"Heterogeneity of non-alcoholic fatty liver disease (NAFLD): Implication for cardiovascular risk stratification","volume":"357","author":"Baratta","year":"2022","journal-title":"Atherosclerosis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000004","article-title":"The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.20776","article-title":"Factors that predict the progression of non-alcoholic fatty liver disease (NAFLD)","volume":"13","author":"Parameswaran","year":"2021","journal-title":"Cureus"},{"key":"B8","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.tibs.2023.10.004","article-title":"UFMylation: a ubiquitin-like modification","volume":"49","author":"Zhou","year":"2024","journal-title":"Trends Biochem Sci"},{"key":"B9","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/cr.2016.39","article-title":"Ubiquitin modifications","volume":"26","author":"Swatek","year":"2016","journal-title":"Cell Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2020.12.005","article-title":"Histone ubiquitination: an integrative signaling platform in genome stability","volume":"37","author":"Mattiroli","year":"2021","journal-title":"Trends Genet"},{"key":"B11","doi-asserted-by":"crossref","DOI":"10.1016\/S0021-9258(20)82050-X","article-title":"Components of ubiquitin-protein ligase system. 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