ArticleCell death & disease2023
Ufmylation on UFBP1 alleviates non-alcoholic fatty liver disease by modulating hepatic endoplasmic reticulum stress.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 24 citations in OpenAlex.
- Narrative review-the emerging role, functions, and mechanisms of UFMylation in cancers.Translational cancer research · 2026Review
- A UFMylation-COPII axis orchestrates lipid transport in intestinal enterocytes and regulates systemic lipid balance.Molecular metabolism · 2026Article
- Injectable pH-responsive carboxymethyl cellulose hydrogel for sustained delivery of IL-22 in the treatment of alcoholic liver disease.Journal of nanobiotechnology · 2026Article
- Ufmylation-Deficient DDRGK1 Ameliorates Obesity by Inhibiting FASN-Mediated Adipocyte Lipogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Huanglian Jiedu Decoction Alleviates Metabolic-Associated Fatty Liver Disease in vivo and in vitro via IRE1α/XBP1s Signaling Pathway.Chinese journal of integrative medicine · 2026Article
- The UFM1 Conjugation System: A Master Regulator of Cellular Stress Surveillance in Human Disease.Biology · 2026Review
- UFMylation in lipid metabolism disorders-associated diseases.Molecular biology reports · 2026Review
- The UFL1-AKT positive feedback loop promotes breast cancer progression by enhancing lipid synthesis.Nature communications · 2026Article
- Exploring the pathogenesis of NAFLD: a study of the correlation of gut microbes and metabolites in humanized mouse gut microbiota.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Unveiling the hidden regulators: how post-translational modifications influence the progression and treatment of hepatocellular carcinoma.Frontiers in oncology · 2026Review
- The beneficial effect of hepatic ER stress-associated protein PDI on obesity-associated glucose dysregulation.Nutrition & metabolism · 2025Article
- DysUFMylation of SREBP1 Promotes the Progression of Hepatocellular Carcinoma by Reprogramming Lipid Metabolism.Journal of clinical and translational hepatology · 2025Article
- MCM5 UFMylation regulates replication origin firing and fork progression.The EMBO journal · 2025Article
- Ufmylation Suppresses Unfolded Protein Response to Prevent Peripartum Cardiomyopathy.JACC. Basic to translational science · 2025Article
- UFMylation System: Biological Functions, Molecular Mechanisms, Diseases, and Drug Discovery.MedComm · 2025Review
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- UFMylation: A supervisor of the HIF1α pathway and a potential therapeutic target for anti-PD-1 combination therapy in hypoxic tumors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Exogenous hydrogen sulfide improves non-alcoholic fatty liver disease by inhibiting endoplasmic reticulum stress/NLRP3 inflammasome pathway.Molecular and cellular biochemistry · 2025Article
- Article
- The ufmylation cascade controls COPII recruitment, anterograde transport, and sorting of nascent GPCRs at ER.Science advances · 2024Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease characterized by lipid accumulation and endoplasmic reticulum (ER) stress, while effective therapies targeting the specific characteristics of NAFLD are limited. Ufmylation is a newly found post-translational modification process that involves the attachment of the Ubiquitin-fold modifier 1 (UFM1) protein to its substrates via ufmylation modification system. Ufmylation regulates ER stress via modifying UFM1 binding protein 1 (UFBP1), suggesting a potential role for ufmylation in NAFLD pathogenesis. However, the precise role of ufmylation in NAFLD remains unclear. Herein, we aim to elucidate the impact of ufmylation on UFBP1 in NAFLD and explore the underlying mechanisms involved. We observed increased expression of UFM1-conjugated proteins and ufmylation modification system components in livers with steatosis derived from NAFLD patients and NAFLD models. Upregulation of ufmylation on hepatic proteins appeared to be an adaptive response to hepatic ER stress in NAFLD. In vitro, knocking down UFBP1 resulted in increased lipid accumulation and lipogenesis in hepatocytes treated with free fatty acids (FFA), which could be rescued by wild-type UFBP1 (WT UFBP1) but not by a mutant form of UFBP1 lacking the main ufmylation site lys267 (UFBP1 K267R). In vivo, ufmylation on UFBP1 ameliorated obesity, hepatic steatosis, hepatic lipogenesis, dyslipidemia, insulin resistance and liver damage in mice with NAFLD induced by a high fat diet (HFD). We also demonstrated that the downregulation of UFBP1 induced ER stress, whereas the reintroduction or overexpression of UFBP1 alleviated ER stress in a manner dependent on ufmylation in NAFLD. This mechanism could be responsible for the amelioration of aberrant hepatic lipogenesis and insulin resistance in NAFLD. Our data reveal a protective role of ufmylation on UFBP1 against NAFLD and offer a specific target for NAFLD treatment.
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