ArticleMolecular metabolism2019
miR-873-5p targets mitochondrial GNMT-Complex II interface contributing to non-alcoholic fatty liver disease.
Article in Molecular metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 48 citations in OpenAlex.
- The Usefulness of Metformin and Ganwei for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Randomized, Placebo-Controlled Trial.International journal of molecular sciences · 2026Trial
- GNMT alleviates heart failure-induced skeletal muscle atrophy by regulating ATP5J2-mediated mitochondrial metabolic reprogramming through succinylation.Apoptosis : an international journal on programmed cell death · 2026Article
- Host Gnmt coordinates with Limosilactobacillus reuteri to alleviate ionizing radiation injury via microbiota remodeling and metabolic regulation in Drosophila melanogaster.Archives of microbiology · 2026Article
- Sulfur amino acid restriction prevents S-adenosylmethionine-driven liver steatosis, hepatocellular carcinoma, and metabolic remodeling in high-fat-fed GNMT-null mice.bioRxiv : the preprint server for biology · 2026Article
- The GNMT N-terminus Couples Folate Feedback to Methyl-donor Homeostasis.bioRxiv : the preprint server for biology · 2026Article
- GNMT and Its Regulatory MicroRNAs as Biomarkers and Therapeutic Targets for Metabolic Dysfunction-Associated Fatty Liver Disease and Hepatocellular Carcinoma.International journal of molecular sciences · 2026Review
- Identification of Circulating MiR-4651 as Novel Biomarker for Metabolic Dysfunction-Associated Steatotic Liver Disease.Gastro hep advances · 2026Article
- Roles of mitochondrial complexes in non-alcoholic fatty liver disease.Frontiers in molecular biosciences · 2026Review
- Choline attenuates NEFA-induced hepatic steatosis via GNMT regulation in hepatocytes.Stress biology · 2025Article
- Dissecting metabolic regulation of behaviors and physiology during aging in Drosophila.Biogerontology · 2025Article
- Investigating the Diagnostic Utility of LncRNA GAS5 in NAFLD Patients.Biomedicines · 2025Article
- Dissecting Metabolic Control of Behaviors and Physiology During Aging in Drosophila.Research square · 2025Article
- The complex role of glycine N-methyltransferase in metabolism-a review.Molecular biology reports · 2025Review
- Anti-miR-873-5p improves alcohol-related liver disease by enhancing hepatic deacetylation via SIRT1.JHEP reports : innovation in hepatology · 2024Article
- Mitochondrial Dysfunction in Metabolic Dysfunction Fatty Liver Disease (MAFLD).International journal of molecular sciences · 2023Review
- ERVK13-1/miR-873-5p/GNMT Axis Promotes Metastatic Potential in Human Bladder Cancer though Sarcosine Production.International journal of molecular sciences · 2023Article
- The Role of Epigenetic Control of Mitochondrial (Dys)Function in MASLD Onset and Progression.Nutrients · 2023Review
- Glutathione Programmed Mitochondria Targeted Delivery of Lonidamine for Effective Against Triple Negative Breast Cancer.International journal of nanomedicine · 2023Article
- Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters.Epigenetics insights · 2023Article
- Review
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Authors and funding
29 authors at 11 institutions in 5 countries.
Funding
Abstract
objectiveNon-alcoholic fatty liver disease (NAFLD) is a complex pathology in which several dysfunctions, including alterations in metabolic pathways, mitochondrial functionality and unbalanced lipid import/export, lead to lipid accumulation and progression to inflammation and fibrosis. The enzyme glycine N-methyltransferase (GNMT), the most important enzyme implicated in S-adenosylmethionine catabolism in the liver, is downregulated during NAFLD progression. We have studied the mechanism involved in GNMT downregulation by its repressor microRNA miR-873-5p and the metabolic pathways affected in NAFLD as well as the benefit of recovery GNMT expression.
methodsmiR-873-5p and GNMT expression were evaluated in liver biopsies of NAFLD/NASH patients. Different in vitro and in vivo NAFLD murine models were used to assess miR-873-5p/GNMT involvement in fatty liver progression through targeting of the miR-873-5p as NAFLD therapy.
resultsWe describe a new function of GNMT as an essential regulator of Complex II activity in the electron transport chain in the mitochondria. In NAFLD, GNMT expression is controlled by miR-873-5p in the hepatocytes, leading to disruptions in mitochondrial functionality in a preclinical murine non-alcoholic steatohepatitis (NASH) model. Upregulation of miR-873-5p is shown in the liver of NAFLD/NASH patients, correlating with hepatic GNMT depletion. Importantly, NASH therapies based on anti-miR-873-5p resolve lipid accumulation, inflammation and fibrosis by enhancing fatty acid β-oxidation in the mitochondria. Therefore, miR-873-5p inhibitor emerges as a potential tool for NASH treatment.
conclusionGNMT participates in the regulation of metabolic pathways and mitochondrial functionality through the regulation of Complex II activity in the electron transport chain. In NAFLD, GNMT is repressed by miR-873-5p and its targeting arises as a valuable therapeutic option for treatment.
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