{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T07:00:36Z","timestamp":1787382036954,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":31,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Melatonin (MLT) has been reported to attenuate Concanavalin A (Con A)\u2010induced acute liver injury via the inhibition of immune cells. Whereas the response of hepatocyte to Con A\u2010caused inflammatory storm and the mechanism of MLT on hepatocyte remain not fully understood. Our RNA\u2010seq and bioinformatic analyses suggested that OPA1 and fatty acid \u03b2\u2010oxidation might be critical. It was found that MLT ameliorated Con A\u2010induced acute liver injury, promoted mitochondrial fusion, fatty acid \u03b2\u2010oxidation, modulated metabolic reprogramming and inhibited apoptosis. The overexpression and knockdown of OPA1 by adenovirus proved that these processes were governed by OPA1. With the overexpression plasmid, agonist, inhibitor and SiRNA, we found that MLT promoted OPA1 upregulation to enhance fatty acid \u03b2\u2010oxidation, which inhibited apoptosis. The MLT and OPA1\u2010promoted fatty acid \u03b2\u2010oxidation enhanced ATP production rather than reduced lipid accumulation. AMPK\/FOXO1 was required for MLT and OPA1\u2010mediated fatty acid \u03b2\u2010oxidation and apoptosis. NOTCH1 was also necessary for this apoptotic process. The results were verified in immune deficiency mice and AML12 cells induced by Con A\u2010stimulated monocyte supernatant. MLT might control the transcription of OPA1 through MEF2A. TOMM70 was critical for MLT translocation and OPA1 upregulation. In conclusion, the present study demonstrated that MLT attenuated Con A\u2010induced acute liver injury via the OPA1\u2010controlled fatty acid \u03b2\u2010oxidation to inhibit apoptosis in hepatocyte.<\/jats:p>","DOI":"10.1111\/jpi.70010","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T04:35:50Z","timestamp":1733114150000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["OPA1 Mediated Fatty Acid \u03b2\u2010Oxidation in Hepatocyte: The Novel Insight for Melatonin Attenuated Apoptosis in Concanavalin A Induced Acute Liver Injury"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9316-7365","authenticated-orcid":false,"given":"Tong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacology China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruonan","family":"Shuang","sequence":"additional","affiliation":[{"name":"School of Integrated Chinese and Western Medicine Nanjing University of Chinese Medicine Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Integrated Chinese and Western Medicine Nanjing University of Chinese Medicine Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Ai","sequence":"additional","affiliation":[{"name":"School of Integrated Chinese and Western Medicine Nanjing University of Chinese Medicine Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichen","family":"Diao","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Technology China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pharmacology China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Tao","sequence":"additional","affiliation":[{"name":"School of Integrated Chinese and Western Medicine Nanjing University of Chinese Medicine Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Huang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Stomatology Nanjing Medical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.02.024"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-13-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.08.004"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.07.021"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202202956"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12812"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI135026"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.02.030"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28031312"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7FO01073G"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-311247"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.108411"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12865"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00084"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17122124"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000568"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2022.07.003"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00506-6"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.04.016"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-022-01076-y"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000000626"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12542"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22081"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1021263"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1219855"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-021-02848-9"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00840-w"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.744838"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.030"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00747-6"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1953-y"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200677200"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14198"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-021-00638-z"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-019-0318-x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2021.02.039"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2013.0583"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2378"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1705768114"}],"container-title":["Journal of Pineal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.70010","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jpi.70010","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.70010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T07:28:16Z","timestamp":1771140496000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jpi.70010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":39,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/jpi.70010"],"URL":"https:\/\/doi.org\/10.1111\/jpi.70010","archive":["Portico"],"relation":{},"ISSN":["0742-3098","1600-079X"],"issn-type":[{"value":"0742-3098","type":"print"},{"value":"1600-079X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"2024-07-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70010"}}