{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:11:17Z","timestamp":1790723477623,"version":"4.1.0"},"reference-count":176,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01AA026759-07"],"award-info":[{"award-number":["5R01AA026759-07"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01AA032010-01A1"],"award-info":[{"award-number":["1R01AA032010-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["3U01AA026817-05"],"award-info":[{"award-number":["3U01AA026817-05"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity, mortality, and premature death worldwide. Its pathogenesis is complex and incompletely understood, with disrupted methionine metabolism as a key contributor. This pathway converts methionine into S-adenosylmethionine (SAM or SAMe), the principal methyl donor, a precursor of glutathione (GSH), and a critical regulator of hepatocellular function. Alterations in methionine metabolism are primarily driven by downregulation of methionine adenosyltransferase 1A (MAT1A), the liver-specific gene encoding the MAT\u03b11 subunit responsible for SAMe biosynthesis. Reduced MAT1A expression and activity lead to hepatic SAMe and GSH deficiency, resulting in global hypomethylation, mitochondrial dysfunction, impaired lipid metabolism, and progressive liver injury, hallmarks of ALD. Recent studies show that MAT\u03b11 also localizes to hepatocyte mitochondria, where its selective depletion contributes to mitochondrial dysfunction in ALD. Experimental models demonstrate that SAMe supplementation restores methylation capacity, replenishes GSH, reduces oxidative stress, and improves mitochondrial function and liver histology. Preservation of mitochondrial MAT\u03b11 also protects against ALD, underscoring its importance in hepatocellular health. Clinical exploration of SAMe in early-stage ALD suggests potential benefit and motivates continued investigation into treatment strategies that build on and extend beyond supplementation. This review summarizes current knowledge on the role of the MAT1A\/SAMe axis in ALD pathophysiology, emphasizing molecular functions and critically evaluating preclinical and clinical evidence for potential therapy.<\/jats:p>","DOI":"10.3390\/antiox14121486","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T11:17:27Z","timestamp":1765451847000},"page":"1486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Methionine Adenosyltransferase 1A and S-Adenosylmethionine in Alcohol-Associated Liver Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Luc\u00eda","family":"Barbier-Torres","sequence":"first","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyoti","family":"Chhimwal","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1264-3153","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Mato","sequence":"additional","affiliation":[{"name":"CIC bioGUNE, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (Ciberehd), Technology, Park of Bizkaia, 48160 Derio,  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelly C.","family":"Lu","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1097\/HEP.0000000000000989","article-title":"Alcohol-Associated Liver Disease and Public Health Policies","volume":"80","author":"Sengupta","year":"2024","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/s41575-023-00759-2","article-title":"Global Epidemiology of Cirrhosis\u2013Aetiology, Trends and Predictions","volume":"20","author":"Huang","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mackowiak, B., Fu, Y., Maccioni, L., and Gao, B. (2024). Alcohol-Associated Liver Disease. J. Clin. Investig., 134.","DOI":"10.1172\/JCI176345"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jun, S., Park, H., Kim, U.-J., Choi, E.J., Lee, H.A., Park, B., Lee, S.Y., Jee, S.H., and Park, H. (2023). Cancer Risk Based on Alcohol Consumption Levels: A Comprehensive Systematic Review and Meta-Analysis. Epidemiol. Health, 45.","DOI":"10.4178\/epih.e2023092"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1161\/HYPERTENSIONAHA.124.22703","article-title":"Alcohol Intake and Risk of Hypertension: A Systematic Review and Dose-Response Meta-Analysis of Nonexperimental Cohort Studies","volume":"81","author":"Cecchini","year":"2024","journal-title":"Hypertension"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1097\/HEP.0000000000000899","article-title":"Alcohol-Associated Liver Disease-Global Epidemiology","volume":"80","author":"Jiang","year":"2024","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1056\/NEJMra2207599","article-title":"Alcohol-Associated Hepatitis","volume":"387","author":"Bataller","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1146\/annurev-pathmechdis-031521-030435","article-title":"Recent Advances in Understanding of Pathogenesis of Alcohol-Associated Liver Disease","volume":"18","author":"Wu","year":"2023","journal-title":"Annu. Rev. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1097\/HEP.0000000000000986","article-title":"Alcohol-Associated Liver Disease: Emerging Therapeutic Strategies","volume":"80","author":"Mullish","year":"2024","journal-title":"Hepatology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.jhep.2010.05.030","article-title":"Enteral Nutrition with or without N-Acetylcysteine in the Treatment of Severe Acute Alcoholic Hepatitis: A Randomized Multicenter Controlled Trial","volume":"53","author":"Moreno","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S1665-2681(19)30863-4","article-title":"Treatment with Metadoxine and Its Impact on Early Mortality in Patients with Severe Alcoholic Hepatitis","volume":"13","year":"2014","journal-title":"Ann. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Marot, A., Singal, A.K., Moreno, C., and Deltenre, P. (2020). Granulocyte Colony-Stimulating Factor for Alcoholic Hepatitis: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. JHEP Rep., 2.","DOI":"10.1016\/j.jhepr.2020.100139"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1002\/hep.31046","article-title":"An Open-Label, Dose-Escalation Study to Assess the Safety and Efficacy of IL-22 Agonist F-652 in Patients With Alcohol-Associated Hepatitis","volume":"72","author":"Arab","year":"2020","journal-title":"Hepatology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1002\/hep.23837","article-title":"Interleukin-22 Treatment Ameliorates Alcoholic Liver Injury in a Murine Model of Chronic-Binge Ethanol Feeding: Role of Signal Transducer and Activator of Transcription 3","volume":"52","author":"Ki","year":"2010","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1002\/hep.20206","article-title":"A Double-Blind Randomized Controlled Trial of Infliximab Associated with Prednisolone in Acute Alcoholic Hepatitis","volume":"39","author":"Naveau","year":"2004","journal-title":"Hepatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1053\/j.gastro.2008.08.057","article-title":"A Randomized, Double-Blinded, Placebo-Controlled Multicenter Trial of Etanercept in the Treatment of Alcoholic Hepatitis","volume":"135","author":"Boetticher","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1097\/MEG.0000000000000458","article-title":"Effects of Probiotics (Cultured Lactobacillus Subtilis\/Streptococcus Faecium) in the Treatment of Alcoholic Hepatitis: Randomized-Controlled Multicenter Study","volume":"27","author":"Han","year":"2015","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s12664-018-0859-4","article-title":"Corticosteroids, Nutrition, Pentoxifylline, or Fecal Microbiota Transplantation for Severe Alcoholic Hepatitis","volume":"37","author":"Philips","year":"2018","journal-title":"Indian. J. Gastroenterol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.cgh.2016.10.029","article-title":"Healthy Donor Fecal Microbiota Transplantation in Steroid-Ineligible Severe Alcoholic Hepatitis: A Pilot Study","volume":"15","author":"Philips","year":"2017","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Michalak, A., Lach, T., and Cicho\u017c-Lach, H. (2021). Oxidative Stress-A Key Player in the Course of Alcohol-Related Liver Disease. J. Clin. Med., 10.","DOI":"10.3390\/jcm10143011"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"332","DOI":"10.4254\/wjh.v12.i7.332","article-title":"Oxidative Stress in Alcohol-Related Liver Disease","volume":"12","author":"Tan","year":"2020","journal-title":"World J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.jhep.2018.10.037","article-title":"Effect of Ethanol on Lipid Metabolism","volume":"70","author":"You","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.3748\/wjg.v20.i9.2136","article-title":"Role of Mitochondria in Alcoholic Liver Disease","volume":"20","author":"Nassir","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Thoudam, T., Gao, H., Jiang, Y., Huda, N., Yang, Z., Ma, J., and Liangpunsakul, S. (2024). Mitochondrial Quality Control in Alcohol-Associated Liver Disease. Hepatol. Commun., 8.","DOI":"10.1097\/HC9.0000000000000534"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.cld.2024.06.005","article-title":"Pathogenesis of Alcohol-Associated Liver Disease","volume":"28","author":"Mandrekar","year":"2024","journal-title":"Clin. Liver Dis."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Yang, T., Gu, Z., Feng, J., Shan, J., Qian, C., and Zhuang, N. (2025). Non-Parenchymal Cells: Key Targets for Modulating Chronic Liver Diseases. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1576739"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/j.jhep.2009.03.007","article-title":"Signalling Pathways in Alcohol-Induced Liver Inflammation","volume":"50","author":"Mandrekar","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1002\/hep.27489","article-title":"Dysbiosis-Induced Intestinal Inflammation Activates TNFRI and Mediates Alcoholic Liver Disease in Mice","volume":"61","author":"Chen","year":"2015","journal-title":"Hepatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.3748\/wjg.v16.i11.1321","article-title":"Alcoholic Liver Disease and the Gut-Liver Axis","volume":"16","author":"Szabo","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4291\/wjgp.v7.i1.17","article-title":"Adipose Tissue-Liver Axis in Alcoholic Liver Disease","volume":"7","author":"Wang","year":"2016","journal-title":"World J. Gastrointest. Pathophysiol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Patidar, P., Hirani, N., Bharti, S., and Baig, M.S. (2024). Key Regulators of Hepatic Stellate Cell Activation in Alcohol Liver Disease: A Comprehensive Review. Int. Immunopharmacol., 141.","DOI":"10.1016\/j.intimp.2024.112938"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ramos-Tovar, E., and Muriel, P. (2020). Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver. Antioxidants, 9.","DOI":"10.3390\/antiox9121279"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.livres.2025.04.007","article-title":"Non-Coding RNAs in Alcohol-Associated Liver Disease","volume":"9","author":"Zeng","year":"2025","journal-title":"Liver Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Habash, N.W., Sehrawat, T.S., Shah, V.H., and Cao, S. (2022). Epigenetics of Alcohol-Related Liver Diseases. JHEP Rep., 4.","DOI":"10.1016\/j.jhepr.2022.100466"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jhep.2019.03.020","article-title":"The Circadian Clock and Liver Function in Health and Disease","volume":"71","author":"Mukherji","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"C1158","DOI":"10.1152\/ajpcell.00551.2022","article-title":"Circadian Regulation of Liver Metabolism: Experimental Approaches in Human, Rodent, and Cellular Models","volume":"325","author":"Daniels","year":"2023","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Summa, K.C., Voigt, R.M., Forsyth, C.B., Shaikh, M., Cavanaugh, K., Tang, Y., Vitaterna, M.H., Song, S., Turek, F.W., and Keshavarzian, A. (2013). Disruption of the Circadian Clock in Mice Increases Intestinal Permeability and Promotes Alcohol-Induced Hepatic Pathology and Inflammation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067102"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"G364","DOI":"10.1152\/ajpgi.00010.2018","article-title":"Emerging Role of Circadian Clock Disruption in Alcohol-Induced Liver Disease","volume":"315","author":"Bailey","year":"2018","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1152\/physrev.00047.2011","article-title":"S-Adenosylmethionine in Liver Health, Injury, and Cancer","volume":"92","author":"Lu","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.livsci.2007.07.005","article-title":"Methionine: A Metabolically Unique Amino Acid","volume":"112","author":"Brosnan","year":"2007","journal-title":"Livest. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4300","DOI":"10.3748\/wjg.v25.i31.4300","article-title":"Methionine Adenosyltransferases in Liver Cancer","volume":"25","author":"Murray","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1515\/CCLM.2007.341","article-title":"Metabolic Regulatory Properties of S-Adenosylmethionine and S-Adenosylhomocysteine","volume":"45","author":"Finkelstein","year":"2007","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3631","DOI":"10.1073\/pnas.81.12.3631","article-title":"Glycine N-Methyltransferase Is a Folate Binding Protein of Rat Liver Cytosol","volume":"81","author":"Cook","year":"1984","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3447","DOI":"10.1016\/S0021-9258(18)34798-7","article-title":"Purification and Properties of Glycine N-Methyltransferase from Rat Liver","volume":"257","author":"Ogawa","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Takusagawa, F., Ogawa, H., and Fujioka, M. (1999). Glycine N-Methyltransferase, a Tetrameric Enzyme. S-Adenosylmethionine-Dependent Methyltransferases, World Scientific.","DOI":"10.1142\/9789812813077_0004"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1023\/B:BOLI.0000009978.17777.33","article-title":"Glycine N-Methyltransferase Deficiency: A New Patient with a Novel Mutation","volume":"26","author":"Luka","year":"2003","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"22507","DOI":"10.1074\/jbc.R109.019273","article-title":"Glycine N-Methyltransferase and Regulation of S-Adenosylmethionine Levels","volume":"284","author":"Luka","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s11248-006-0008-1","article-title":"A Glycine N-Methyltransferase Knockout Mouse Model for Humans with Deficiency of This Enzyme","volume":"15","author":"Luka","year":"2006","journal-title":"Transgenic Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1002\/hep.21863","article-title":"Glycine N-Methyltransferase\u2212\/\u2212 Mice Develop Chronic Hepatitis and Glycogen Storage Disease in the Liver","volume":"46","author":"Liu","year":"2007","journal-title":"Hepatology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1002\/hep.22159","article-title":"Loss of the Glycine N-Methyltransferase Gene Leads to Steatosis and Hepatocellular Carcinoma in Mice","volume":"47","author":"Ariz","year":"2008","journal-title":"Hepatology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1016\/j.cmet.2025.08.001","article-title":"Homocysitaconate Controls Inflammation through Reshaping Methionine Metabolism and N-Homocysteinylation","volume":"37","author":"Lin","year":"2025","journal-title":"Cell Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0016-5085(98)70494-9","article-title":"Methionine Adenosyltransferase and Liver Disease: It\u2019s All about SAM","volume":"114","author":"Lu","year":"1998","journal-title":"Gastroenterology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0163-7258(96)00197-0","article-title":"S-Adenosylmethionine Synthesis: Molecular Mechanisms and Clinical Implications","volume":"73","author":"Mato","year":"1997","journal-title":"Pharmacol. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/0016-5085(81)90489-3","article-title":"Evidence for Impairment of Transsulfuration Pathway in Cirrhosis","volume":"81","author":"Horowitz","year":"1981","journal-title":"Gastroenterology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"G178","DOI":"10.1152\/ajpgi.2000.279.1.G178","article-title":"Changes in Methionine Adenosyltransferase and S-Adenosylmethionine Homeostasis in Alcoholic Rat Liver","volume":"279","author":"Lu","year":"2000","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1111\/j.1530-0277.1993.tb00798.x","article-title":"Dietary Betaine Promotes Generation of Hepatic S-Adenosylmethionine and Protects the Liver from Ethanol-Induced Fatty Infiltration","volume":"17","author":"Barak","year":"1993","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1002\/hep.1840180433","article-title":"The Effect of Ethanol on One-Carbon Metabolism: Increased Methionine Catabolism and Lipotrope Methyl-Group Wastage","volume":"18","author":"Trimble","year":"1993","journal-title":"Hepatology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/hep.1840110203","article-title":"S-Adenosyl-L-Methionine Attenuates Alcohol-Induced Liver Injury in the Baboon","volume":"11","author":"Lieber","year":"1990","journal-title":"Hepatology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.jhep.2006.08.024","article-title":"Betaine Attenuates Alcoholic Steatosis by Restoring Phosphatidylcholine Generation via the Phosphatidylethanolamine Methyltransferase Pathway","volume":"46","author":"Kharbanda","year":"2007","journal-title":"J. Hepatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1097\/01.ALC.0000108654.77178.03","article-title":"Abnormal Hepatic Methionine and Glutathione Metabolism in Patients with Alcoholic Hepatitis","volume":"28","author":"Lee","year":"2004","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/hep.1840160225","article-title":"Increased 4-Hydroxynonenal Levels in Experimental Alcoholic Liver Disease: Association of Lipid Peroxidation with Liver Fibrogenesis","volume":"16","author":"Kamimura","year":"1992","journal-title":"Hepatology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.redox.2016.08.005","article-title":"The Methyl Donor S-Adenosylmethionine Prevents Liver Hypoxia and Dysregulation of Mitochondrial Bioenergetic Function in a Rat Model of Alcohol-Induced Fatty Liver Disease","volume":"9","author":"King","year":"2016","journal-title":"Redox Biol."},{"key":"ref_63","first-page":"207","article-title":"Feeding S-Adenosyl-L-Methionine Attenuates Both Ethanol-Induced Depletion of Mitochondrial Glutathione and Mitochondrial Dysfunction in Periportal and Perivenous Rat Hepatocytes","volume":"21","author":"Morales","year":"1995","journal-title":"Hepatology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/0041-008X(86)90310-8","article-title":"Effect of the Variations of S-Adenosyl-L-Methionine Liver Content on Fat Accumulation and Ethanol Metabolism in Ethanol-Intoxicated Rats","volume":"83","author":"Feo","year":"1986","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_65","first-page":"699","article-title":"Transport of Reduced Glutathione in Hepatic Mitochondria and Mitoplasts from Ethanol-Treated Rats: Effect of Membrane Physical Properties and S-Adenosyl-L-Methionine","volume":"26","author":"Colell","year":"1997","journal-title":"Hepatology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/S0955-2863(03)00116-5","article-title":"S-Adenosylmethionine (SAMe) Protects against Acute Alcohol Induced Hepatotoxicity in Mice","volume":"14","author":"Song","year":"2003","journal-title":"J. Nutr. Biochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"G857","DOI":"10.1152\/ajpgi.00044.2006","article-title":"S-Adenosylmethionine Prevents Chronic Alcohol-Induced Mitochondrial Dysfunction in the Rat Liver","volume":"291","author":"Bailey","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1111\/j.1530-0277.2007.00511.x","article-title":"S-Adenosylmethionine Attenuates Oxidative Liver Injury in Micropigs Fed Ethanol with a Folate-Deficient Diet","volume":"31","author":"Villanueva","year":"2007","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/S0168-8278(99)80263-3","article-title":"S-Adenosylmethionine in Alcoholic Liver Cirrhosis: A Randomized, Placebo-Controlled, Double-Blind, Multicenter Clinical Trial","volume":"30","author":"Mato","year":"1999","journal-title":"J. Hepatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/S0168-8278(00)80122-1","article-title":"Reduced mRNA Abundance of the Main Enzymes Involved in Methionine Metabolism in Human Liver Cirrhosis and Hepatocellular Carcinoma","volume":"33","author":"Avila","year":"2000","journal-title":"J. Hepatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/hep.20168","article-title":"Hepatic Transmethylation Reactions in Micropigs with Alcoholic Liver Disease","volume":"39","author":"Villanueva","year":"2004","journal-title":"Hepatology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/0006-291X(74)90988-7","article-title":"Ethanol-Induced Changes in Methionine Metabolism in Rat Liver","volume":"61","author":"Finkelstein","year":"1974","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/hep.510230314","article-title":"Ethanol Feeding of Micropigs Alters Methionine Metabolism and Increases Hepatocellular Apoptosis and Proliferation","volume":"23","author":"Halsted","year":"1996","journal-title":"Hepatology"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Agudo, R., Gonz\u00e1lez-Recio, I., Serrano-Maci\u00e1, M., Bravo, M., Petrov, P., Blaya, D., Herranz, J.M., Mercado-G\u00f3mez, M., Rejano-Gordillo, C.M., and Lachiondo-Ortega, S. (2024). Anti-miR-873-5p Improves Alcohol-Related Liver Disease by Enhancing Hepatic Deacetylation via SIRT1. JHEP Rep., 6.","DOI":"10.1016\/j.jhepr.2023.100918"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"421","DOI":"10.3945\/an.111.000661","article-title":"Vitamin-Dependent Methionine Metabolism and Alcoholic Liver Disease","volume":"2","author":"Halsted","year":"2011","journal-title":"Adv. Nutr."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/hep.510300134","article-title":"Effect of Ethanol and High-Fat Feeding on Hepatic Gamma-Glutamylcysteine Synthetase Subunit Expression in the Rat","volume":"30","author":"Lu","year":"1999","journal-title":"Hepatology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1002\/hep.21650","article-title":"Role of S-Adenosyl-L-Methionine in Liver Health and Injury","volume":"45","author":"Mato","year":"2007","journal-title":"Hepatology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/0955-2863(90)90070-2","article-title":"Methionine Metabolism in Mammals","volume":"1","author":"Finkelstein","year":"1990","journal-title":"J. Nutr. Biochem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/0026-0495(75)90040-2","article-title":"Labile Methyl Balances for Normal Humans on Various Dietary Regimens","volume":"24","author":"Mudd","year":"1975","journal-title":"Metabolism"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3347","DOI":"10.1096\/fj.09-130187","article-title":"Conformational Signals in the C-Terminal Domain of Methionine Adenosyltransferase I\/III Determine Its Nucleocytoplasmic Distribution","volume":"23","author":"Reytor","year":"2009","journal-title":"FASEB J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1002\/hep.30762","article-title":"Methionine Adenosyltransferase A1 Is Targeted to the Mitochondrial Matrix and Interacts with Cytochrome P450 2E1 to Lower Its Expression","volume":"70","author":"Murray","year":"2019","journal-title":"Hepatology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1042\/bj3420021","article-title":"S-Adenosylmethionine Attenuates the Lipopolysaccharide-Induced Expression of the Gene for Tumour Necrosis Factor Alpha","volume":"342","author":"Watson","year":"1999","journal-title":"Biochem. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1002\/hep.22231","article-title":"S-Adenosylmethionine Inhibits Lipopolysaccharide-Induced Gene Expression via Modulation of Histone Methylation","volume":"47","author":"Ara","year":"2008","journal-title":"Hepatology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/hep.20274","article-title":"S-Adenosylmethionine and Its Metabolite Induce Apoptosis in HepG2 Cells: Role of Protein Phosphatase 1 and Bcl-x(S)","volume":"40","author":"Yang","year":"2004","journal-title":"Hepatology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5560","DOI":"10.1073\/pnas.091016398","article-title":"Methionine Adenosyltransferase 1A Knockout Mice Are Predisposed to Liver Injury and Exhibit Increased Expression of Genes Involved in Proliferation","volume":"98","author":"Lu","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1096\/fj.02-0078fje","article-title":"Spontaneous Oxidative Stress and Liver Tumors in Mice Lacking Methionine Adenosyltransferase 1A","volume":"16","author":"Corrales","year":"2002","journal-title":"FASEB J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1073\/pnas.0536625100","article-title":"Functional Proteomics of Nonalcoholic Steatohepatitis: Mitochondrial Proteins as Targets of S-Adenosylmethionine","volume":"100","author":"Avila","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Robinson, A.E., Binek, A., Ramani, K., Sundararaman, N., Barbier-Torres, L., Murray, B., Venkatraman, V., Kreimer, S., Ardle, A.M., and Noureddin, M. (2023). Hyperphosphorylation of Hepatic Proteome Characterizes Nonalcoholic Fatty Liver Disease in S-Adenosylmethionine Deficiency. iScience, 26.","DOI":"10.1016\/j.isci.2023.105987"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Floris, A., Chandla, S., Lim, Y., Barbier-Torres, L., Seth, K., Khangholi, A., Li, T.W.H., Robison, A., Murray, B.J., and Lee, S. (2024). Sumoylation of Methionine Adenosyltransferase Alpha 1 Promotes Mitochondrial Dysfunction in Alcohol-Associated Liver Disease. Hepatology, 80.","DOI":"10.1097\/HEP.0000000000000717"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1053\/j.gastro.2008.09.026","article-title":"S-Adenosylmethionine Regulates Apurinic\/Apyrimidinic Endonuclease 1 Stability: Implication in Hepatocarcinogenesis","volume":"136","author":"Tomasi","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1002\/hep.22141","article-title":"Expansion of Liver Cancer Stem Cells during Aging in Methionine Adenosyltransferase 1A-Deficient Mice","volume":"47","author":"Rountree","year":"2008","journal-title":"Hepatology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1002\/hep.23530","article-title":"S-Adenosylmethionine Regulates Dual-Specificity Mitogen-Activated Protein Kinase Phosphatase Expression in Mouse and Human Hepatocytes","volume":"51","author":"Tomasi","year":"2010","journal-title":"Hepatology"},{"key":"ref_93","first-page":"608","article-title":"Evidence for an LKB1\/AMPK\/eNOS Cascade Regulated by HGF, S-Adenosylmethionine and NO in Hepatocyte Proliferation","volume":"49","author":"Ariz","year":"2009","journal-title":"Hepatology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1053\/j.gastro.2017.01.015","article-title":"Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis","volume":"152","author":"Alonso","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Alarc\u00f3n-Vila, C., Insausti-Urkia, N., Torres, S., Segal\u00e9s-Rovira, P., Conde de la Rosa, L., Nu\u00f1ez, S., Fucho, R., Fern\u00e1ndez-Checa, J.C., and Garc\u00eda-Ruiz, C. (2023). Dietary and Genetic Disruption of Hepatic Methionine Metabolism Induce Acid Sphingomyelinase to Promote Steatohepatitis. Redox Biol., 59.","DOI":"10.1016\/j.redox.2022.102596"},{"key":"ref_96","first-page":"101","article-title":"Glycine N-Methyltransferase Deficiency: A Member of Dysmethylating Liver Disorders?","volume":"31","author":"Erdol","year":"2016","journal-title":"JIMD Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"G732","DOI":"10.1152\/ajpgi.00332.2009","article-title":"Analysis of the Liver Mitochondrial Proteome in Response to Ethanol and S-Adenosylmethionine Treatments: Novel Molecular Targets of Disease and Hepatoprotection","volume":"298","author":"Andringa","year":"2010","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/BF03258362","article-title":"Effect of Ethanol Consumption on Metabolism of S-Adenosyl-L-Methionine in Rat Liver","volume":"4","author":"Chawla","year":"1992","journal-title":"Drug Investig."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1530-0277.2008.00803.x","article-title":"S-Adenosyl-L-Methionine Co-Administration Prevents the Ethanol-Elicited Dissociation of Hepatic Mitochondrial Ribosomes in Male Rats","volume":"33","author":"Sykora","year":"2009","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1093\/alcalc\/agg066","article-title":"Polyenylphosphatidylcholine Corrects The Alcohol-Induced Hepatic Oxidative Stress By Restoring S-Adenosylmethionine","volume":"38","author":"Aleynik","year":"2003","journal-title":"Alcohol. Alcohol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.bbadis.2011.01.016","article-title":"Ethanol Exposure Modulates Hepatic S-Adenosylmethionine and S-Adenosylhomocysteine Levels in the Isolated Perfused Rat Liver through Changes in the Redox State of the NADH\/NAD+ System","volume":"1812","author":"Watson","year":"2011","journal-title":"Biochim. et Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.bcp.2007.05.005","article-title":"Alcohol-Induced S-Adenosylhomocysteine Accumulation in the Liver Sensitizes to TNF Hepatotoxicity: Possible Involvement of Mitochondrial S-Adenosylmethionine Transport","volume":"74","author":"Song","year":"2007","journal-title":"Biochem. Pharmacol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"6489","DOI":"10.1073\/pnas.0509531103","article-title":"S-Adenosylmethionine Stabilizes Cystathionine \u03b2-Synthase and Modulates Redox Capacity","volume":"103","author":"Prudova","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Barbier-Torres, L., Murray, B., Yang, J.W., Wang, J., Matsuda, M., Robinson, A., Binek, A., Fan, W., Fern\u00e1ndez-Ramos, D., and Lopitz-Otsoa, F. (2022). Depletion of Mitochondrial Methionine Adenosyltransferase A1 Triggers Mitochondrial Dysfunction in Alcohol-Associated Liver Disease. Nat. Commun., 13.","DOI":"10.1038\/s41467-022-28201-2"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Schober, F.A., Moore, D., Atanassov, I., Moedas, M.F., Clemente, P., V\u00e9gv\u00e1ri, \u00c1., Fissi, N.E., Filograna, R., Bucher, A.-L., and Hinze, Y. (2021). The One-Carbon Pool Controls Mitochondrial Energy Metabolism via Complex I and Iron-Sulfur Clusters. Sci. Adv., 7.","DOI":"10.1126\/sciadv.abf0717"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S0005-2760(97)00108-2","article-title":"Phosphatidylethanolamine N-Methyltransferase from Liver","volume":"1348","author":"Vance","year":"1997","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"P\u00e9rez, C., P\u00e9rez-Z\u00fa\u00f1iga, F.J., Garrido, F., Reytor, E., Portillo, F., and Pajares, M.A. (2016). The Oncogene PDRG1 Is an Interaction Target of Methionine Adenosyltransferases. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163761"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1002\/hep.28964","article-title":"Prohibitin 1 Suppresses Liver Cancers Tumorigenesis in Mice and Human Hepatocellular and Cholangiocarcinoma Cells","volume":"65","author":"Fan","year":"2017","journal-title":"Hepatology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1042\/bj3460475","article-title":"Cloning and Functional Characterization of the 5\u2032-Flanking Region of Human Methionine Adenosyltransferase 1A Gene","volume":"346 Pt. 2","author":"Zeng","year":"2000","journal-title":"Biochem. J."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1016\/j.biocel.2008.02.004","article-title":"Involvement of CCAAT\/Enhancer Binding Protein-Beta (C\/EBPbeta) in Epigenetic Regulation of Mouse Methionine Adenosyltransferase 1A Gene Expression","volume":"40","author":"Ikeda","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1096\/fasebj.14.1.95","article-title":"Liver-Specific Methionine Adenosyltransferase MAT1A Gene Expression Is Associated with a Specific Pattern of Promoter Methylation and Histone Acetylation: Implications for MAT1A Silencing during Transformation","volume":"14","author":"Torres","year":"2000","journal-title":"FASEB J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1053\/j.gastro.2018.04.032","article-title":"Mechanisms of MAFG Dysregulation in Cholestatic Liver Injury and Development of Liver Cancer","volume":"155","author":"Liu","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1002\/hep.28541","article-title":"Deregulated Methionine Adenosyltransferase A1, c-Myc, and Maf Proteins Together Promote Cholangiocarcinoma Growth in Mice and Humans(\u2021)","volume":"64","author":"Yang","year":"2016","journal-title":"Hepatology"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1053\/j.gastro.2010.01.032","article-title":"HuR\/Methyl-HuR and AUF1 Regulate the MAT Expressed during Liver Proliferation, Differentiation, and Carcinogenesis","volume":"138","author":"Embade","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1002\/mc.21861","article-title":"Role of Epigenetic and miR-22 and miR-29b Alterations in the Downregulation of Mat1a and Mthfr Genes in Early Preneoplastic Livers in Rats Induced by 2-Acetylaminofluorene","volume":"52","author":"Koturbash","year":"2013","journal-title":"Mol. Carcinog."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1172\/JCI63861","article-title":"MicroRNAs Regulate Methionine Adenosyltransferase 1A Expression in Hepatocellular Carcinoma","volume":"123","author":"Yang","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"104772","DOI":"10.18632\/oncotarget.18300","article-title":"Tumor-Suppressive Effect of S-Adenosylmethionine Supplementation in a Murine Model of Inflammation-Mediated Hepatocarcinogenesis Is Dependent on Treatment Longevity","volume":"8","author":"Stoyanov","year":"2017","journal-title":"Oncotarget"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1096\/fasebj.11.12.9337154","article-title":"Interaction of Liver Methionine Adenosyltransferase with Hydroxyl Radical","volume":"11","author":"Ruiz","year":"1997","journal-title":"FASEB J."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1002\/hep.510280420","article-title":"Nitric Oxide Inactivates Rat Hepatic Methionine Adenosyltransferase In Vivo by S-Nitrosylation","volume":"28","author":"Ruiz","year":"1998","journal-title":"Hepatology"},{"key":"ref_120","first-page":"391","article-title":"Regulation of Rat Liver S-Adenosylmethionine Synthetase during Septic Shock: Role of Nitric Oxide","volume":"25","author":"Avila","year":"1997","journal-title":"Hepatology"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1042\/bj3030949","article-title":"Protein Kinase C Phosphorylation of Rat Liver S-Adenosylmethionine Synthetase: Dissociation and Production of an Active Monomer","volume":"303 Pt. 3","author":"Pajares","year":"1994","journal-title":"Biochem. J."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"5866","DOI":"10.1038\/s41388-021-01980-6","article-title":"Deregulated 14-3-3\u03b6 and Methionine Adenosyltransferase A1 Interplay Promotes Liver Cancer Tumorigenesis in Mice and Humans","volume":"40","author":"Lu","year":"2021","journal-title":"Oncogene"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1111\/j.1530-0277.1994.tb00915.x","article-title":"Hepatic Phosphatidylethanolamine Methyltransferase Activity Is Decreased by Ethanol and Increased by Phosphatidylcholine","volume":"18","author":"Lieber","year":"1994","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1055\/s-0029-1214371","article-title":"Alcoholic Liver Disease and Methionine Metabolism","volume":"29","author":"Kharbanda","year":"2009","journal-title":"Semin. Liver Dis."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"10072","DOI":"10.1073\/pnas.112336399","article-title":"Folate Deficiency Disturbs Hepatic Methionine Metabolism and Promotes Liver Injury in the Ethanol-Fed Micropig","volume":"99","author":"Halsted","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.jhep.2010.07.027","article-title":"Aberrant DNA Methylation Distinguishes Hepatocellular Carcinoma Associated with HBV and HCV Infection and Alcohol Intake","volume":"54","author":"Lambert","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1111\/acer.12405","article-title":"Methylation and Gene Expression Responses to Ethanol Feeding and Betaine Supplementation in the Cystathionine Beta Synthase-Deficient Mouse","volume":"38","author":"Medici","year":"2014","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"9425","DOI":"10.18632\/oncotarget.2444","article-title":"Epigenetic Signatures of Alcohol Abuse and Hepatitis Infection during Human Hepatocarcinogenesis","volume":"5","author":"Hlady","year":"2014","journal-title":"Oncotarget"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.3748\/wjg.v12.i15.2375","article-title":"Expression and Activity of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase Correlate with Ethanol-Induced Liver Injury","volume":"12","author":"Yuan","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1089\/dna.2022.0669","article-title":"Hypomethylation of Long Interspersed Nucleotide Elements and Aldehyde Dehydrogenase in Patients of Alcohol Use Disorder with Cirrhosis","volume":"42","author":"Shankarappa","year":"2023","journal-title":"DNA Cell Biol."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zhang, S., Xie, X., Chen, Z., Wu, L., Yu, Z., Guo, X., and Chen, G. (2020). Association of TNFRSF12A Methylation With Prognosis in Hepatocellular Carcinoma With History of Alcohol Consumption. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.01299"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"G54","DOI":"10.1152\/ajpgi.00542.2004","article-title":"Chronic Ethanol Feeding and Folate Deficiency Activate Hepatic Endoplasmic Reticulum Stress Pathway in Micropigs","volume":"289","author":"Esfandiari","year":"2005","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1111\/j.1530-0277.2007.00407.x","article-title":"S-Adenosylmethionine Attenuates Hepatic Lipid Synthesis in Micropigs Fed Ethanol with a Folate-Deficient Diet","volume":"31","author":"Esfandiari","year":"2007","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1002\/hep.31800","article-title":"Stress-Responsive Gene FK506-Binding Protein 51 Mediates Alcohol-Induced Liver Injury Through the Hippo Pathway and Chemokine (C-X-C Motif) Ligand 1 Signaling","volume":"74","author":"Kusumanchi","year":"2021","journal-title":"Hepatology"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Zeybel, M., Hardy, T., Robinson, S.M., Fox, C., Anstee, Q.M., Ness, T., Masson, S., Mathers, J.C., French, J., and White, S. (2015). Differential DNA Methylation of Genes Involved in Fibrosis Progression in Non-Alcoholic Fatty Liver Disease and Alcoholic Liver Disease. Clin. Epigenetics, 7.","DOI":"10.1186\/s13148-015-0056-6"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.yexmp.2015.08.001","article-title":"Increased DNA Methylation in the Livers of Patients with Alcoholic Hepatitis","volume":"99","author":"Shen","year":"2015","journal-title":"Exp. Mol. Pathol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1093\/toxsci\/kfq031","article-title":"Mechanism for Prevention of Alcohol-Induced Liver Injury by Dietary Methyl Donors","volume":"115","author":"Powell","year":"2010","journal-title":"Toxicol. Sci."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Cruise, T.M., Kotlo, K., Malovic, E., and Pandey, S.C. (2023). Advances in DNA, Histone, and RNA Methylation Mechanisms in the Pathophysiology of Alcohol Use Disorder. Adv. Drug Alcohol. Res., 3.","DOI":"10.3389\/adar.2023.10871"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.lfs.2007.07.030","article-title":"Distinct Methylation Patterns in Histone H3 at Lys-4 and Lys-9 Correlate with up- & down-Regulation of Genes by Ethanol in Hepatocytes","volume":"81","author":"Bhadra","year":"2007","journal-title":"Life Sci."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"47","DOI":"10.35946\/arcr.v35.1.06","article-title":"Epigenetic Effects of Ethanol on the Liver and Gastrointestinal System","volume":"35","author":"Shukla","year":"2013","journal-title":"Alcohol. Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1111\/j.1530-0277.2008.00885.x","article-title":"Chronic Ethanol Feeding Alters Hepatocyte Memory Which Is Not Altered by Acute Feeding","volume":"33","author":"Oliva","year":"2009","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"G352","DOI":"10.1152\/ajpgi.00316.2003","article-title":"Inhibition of Lipopolysaccharide-Stimulated TNF-Alpha Promoter Activity by S-Adenosylmethionine and 5\u2032-Methylthioadenosine","volume":"287","author":"Veal","year":"2004","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.ajpath.2012.06.010","article-title":"Epigenetic Regulation of miR-34a Expression in Alcoholic Liver Injury","volume":"181","author":"Meng","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Barcena-Varela, M., Colyn, L., and Fernandez-Barrena, M.G. (2019). Epigenetic Mechanisms in Hepatic Stellate Cell Activation During Liver Fibrosis and Carcinogenesis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102507"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ejphar.2004.12.041","article-title":"Effect of S-Adenosyl-L-Methionine on the Activation, Proliferation and Contraction of Hepatic Stellate Cells","volume":"509","author":"Matsui","year":"2005","journal-title":"Eur. J. Pharmacol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.intimp.2014.01.021","article-title":"S-Adenosylmethionine Inhibits the Activated Phenotype of Human Hepatic Stellate Cells via Rac1 and Matrix Metalloproteinases","volume":"19","author":"Zhang","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1097\/SHK.0b013e318160f417","article-title":"S-Adenosyl-L-Methionine Attenuates Oxidative Stress and Hepatic Stellate Cell Activation in an Ethanol-LPS-Induced Fibrotic Rat Model","volume":"30","author":"Karaa","year":"2008","journal-title":"Shock"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1111\/j.1478-3231.2011.02512.x","article-title":"S-Adenosyl-L-Methionine Inhibits Collagen Secretion in Hepatic Stellate Cells via Increased Ubiquitination","volume":"31","author":"Thompson","year":"2011","journal-title":"Liver Int."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.tem.2016.10.004","article-title":"1-Carbon Cycle Metabolites Methylate Their Way to Fatty Liver","volume":"28","author":"Walker","year":"2017","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.7150\/ijbs.90104","article-title":"S-Adenosylmethionine Negatively Regulates the Mitochondrial Respiratory Chain Repressor MCJ in the Liver","volume":"20","author":"Chhimwal","year":"2024","journal-title":"Int. J. Biol. Sci."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Glasgow, R.I.C., Singh, V., Pe\u00f1a-P\u00e9rez, L., Wilhalm, A., Moedas, M.F., Moore, D., Rosenberger, F.A., Li, X., Atanassov, I., and Saba, M. (2025). The Mitochondrial Methylation Potential Gates Mitoribosome Assembly. Nat. Commun., 16.","DOI":"10.1038\/s41467-025-60977-x"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.4049\/jimmunol.181.5.3049","article-title":"TRIF and IRF-3 Binding to the TNF Promoter Results in Macrophage TNF Dysregulation and Steatosis Induced by Chronic Ethanol","volume":"181","author":"Zhao","year":"2008","journal-title":"J. Immunol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1189\/jlb.1005613","article-title":"Chronic Ethanol Feeding Increases Activation of NADPH Oxidase by Lipopolysaccharide in Rat Kupffer Cells: Role of Increased Reactive Oxygen in LPS-Stimulated ERK1\/2 Activation and TNF-\u03b1 Production","volume":"79","author":"Thakur","year":"2006","journal-title":"J. Leukoc. Biol."},{"key":"ref_154","first-page":"G125","article-title":"S-Adenosylmethionine Deficiency and TNF-Alpha in Lipopolysaccharide-Induced Hepatic Injury","volume":"275","author":"Chawla","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0016-5085(99)70566-4","article-title":"An Alcoholic Binge Causes Massive Degradation of Hepatic Mitochondrial DNA in Mice","volume":"117","author":"Mansouri","year":"1999","journal-title":"Gastroenterology"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1016\/0016-5085(86)90253-2","article-title":"Significance of Megamitochondria in Alcoholic Liver Disease","volume":"90","author":"Chedid","year":"1986","journal-title":"Gastroenterology"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1136\/gutjnl-2020-321548","article-title":"ATF4 Activation Promotes Hepatic Mitochondrial Dysfunction by Repressing NRF1-TFAM Signaling in Alcoholic Steatohepatitis","volume":"70","author":"Hao","year":"2021","journal-title":"Gut"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"G954","DOI":"10.1152\/ajpgi.00246.2010","article-title":"Chronic Ethanol Consumption Enhances Sensitivity to Ca(2+)-Mediated Opening of the Mitochondrial Permeability Transition Pore and Increases Cyclophilin D in Liver","volume":"299","author":"King","year":"2010","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"178","DOI":"10.4161\/oxim.3.3.12288","article-title":"Acetaldehyde Adducts in Alcoholic Liver Disease","volume":"3","author":"Setshedi","year":"2010","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1053\/gast.2003.50089","article-title":"Acetaldehyde Impairs Mitochondrial Glutathione Transport in HepG2 Cells through Endoplasmic Reticulum Stress","volume":"124","author":"Lluis","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Cort\u00e9s-Rojo, C., Vargas-Vargas, M.A., Olmos-Orizaba, B.E., Rodr\u00edguez-Orozco, A.R., and Calder\u00f3n-Cort\u00e9s, E. (2020). Interplay between NADH Oxidation by Complex I, Glutathione Redox State and Sirtuin-3, and Its Role in the Development of Insulin Resistance. Biochim. Biophys. Acta Mol. Basis Dis., 1866.","DOI":"10.1016\/j.bbadis.2020.165801"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1053\/j.gastro.2004.09.049","article-title":"The Role of AMP-Activated Protein Kinase in the Action of Ethanol in the Liver","volume":"127","author":"You","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.redox.2018.04.006","article-title":"Nicotinamide Riboside Attenuates Alcohol Induced Liver Injuries via Activation of SirT1\/PGC-1\u03b1\/Mitochondrial Biosynthesis Pathway","volume":"17","author":"Wang","year":"2018","journal-title":"Redox Biol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.bbrc.2008.09.039","article-title":"Ethanol Intoxication Increases Hepatic N-Lysyl Protein Acetylation","volume":"376","author":"Picklo","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1016\/j.cmet.2024.07.024","article-title":"Mitochondrial Membrane Lipids in the Regulation of Bioenergetic Flux","volume":"36","author":"Decker","year":"2024","journal-title":"Cell Metab."},{"key":"ref_166","first-page":"419","article-title":"Ceramide and Sphingosine 1-Phosphate in Liver Diseases","volume":"43","author":"Park","year":"2020","journal-title":"Mol. Cells"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1111\/acer.12315","article-title":"S-Adenosylhomocysteine Inhibits NF\u03baB-Mediated Gene Expression in Hepatocytes and Confers Sensitivity to TNF Cytotoxicity","volume":"38","author":"Watson","year":"2014","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.abb.2008.04.033","article-title":"S-Adenosyl-L-Methionine Decreases the Elevated Hepatotoxicity Induced by Fas Agonistic Antibody plus Acute Ethanol Pretreatment in Mice","volume":"477","author":"Wang","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1023\/A:1026606303738","article-title":"Effect of S-Adenosyl-L-Methionine and Dilinoleoylphosphatidylcholine on Liver Lipid Composition and Ethanol Hepatotoxicity in Isolated Perfused Rat Liver","volume":"43","author":"Gigliozzi","year":"1998","journal-title":"Dig. Dis. Sci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.yexmp.2011.01.005","article-title":"S-Adenosylmethionine Prevents the up Regulation of Toll-like Receptor (TLR) Signaling Caused by Chronic Ethanol Feeding in Rats","volume":"90","author":"Oliva","year":"2011","journal-title":"Exp. Mol. Pathol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1016\/S0016-5085(03)00276-2","article-title":"Betaine Decreases Hyperhomocysteinemia, Endoplasmic Reticulum Stress, and Liver Injury in Alcohol-Fed Mice","volume":"124","author":"Ji","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Kharbanda, K.K., Todero, S.L., King, A.L., Osna, N.A., McVicker, B.L., Tuma, D.J., Wisecarver, J.L., and Bailey, S.M. (2012). Betaine Treatment Attenuates Chronic Ethanol-Induced Hepatic Steatosis and Alterations to the Mitochondrial Respiratory Chain Proteome. Int. J. Hepatol., 2012.","DOI":"10.1155\/2012\/962183"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.etap.2016.05.033","article-title":"Betaine Treatment Decreased Oxidative Stress, Inflammation, and Stellate Cell Activation in Rats with Alcoholic Liver Fibrosis","volume":"45","author":"Uysal","year":"2016","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Arumugam, M.K., Chava, S., Perumal, S.K., Paal, M.C., Rasineni, K., Ganesan, M., Donohue, T.M., Osna, N.A., and Kharbanda, K.K. (2022). Acute Ethanol-Induced Liver Injury Is Prevented by Betaine Administration. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.940148"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"407","DOI":"10.3109\/00365528909093067","article-title":"Effects of Oral S-Adenosyl-L-Methionine on Hepatic Glutathione in Patients with Liver Disease","volume":"24","author":"Vendemiale","year":"1989","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1111\/j.1530-0277.2011.01547.x","article-title":"S-Adenosyl-L-Methionine Treatment for Alcoholic Liver Disease: A Double-Blinded, Randomized, Placebo-Controlled Trial","volume":"35","author":"Medici","year":"2011","journal-title":"Alcohol. Clin. Exp. Res."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/12\/1486\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T11:41:01Z","timestamp":1765453261000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/12\/1486"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,11]]},"references-count":176,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["antiox14121486"],"URL":"https:\/\/doi.org\/10.3390\/antiox14121486","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,11]]}}}