{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T09:29:50Z","timestamp":1784366990675,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T00:00:00Z","timestamp":1743811200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>The membrane protein (M), a key structural protein of SARS\u2010CoV\u20102 that regulates virus assembly and morphogenesis, is involved in the pathological processes of multiple organ damage and metabolic disorders. This study aims to elucidate the mechanisms of M\u2010mediated host ferroptosis and lipid accumulation during SARS\u2010CoV\u20102 infection. Here, we detected that M protein enhances cellular sensitivity to ferroptosis. Additionally, we uncovered the pivotal role of perilipin\u20102 and sterol regulatory element\u2010binding protein 1 in M\u2010induced lipid accumulation. Xanthohumol, a cost\u2010effective and orally available diacylglycerol acyltransferase inhibitor, alleviated triglyceride and total cholesterol accumulation, thereby counteracting the M\u2010induced ferroptosis. Furthermore, we identified that the mitochondrial import inner membrane translocase subunit TIM23 and the mitochondrial import receptor subunit TOM20 homolog contribute to M\u2010induced mitochondrial dysfunction. Notably, inhibiting lipid synthesis effectively reduced mitochondrial reactive oxygen species and transmembrane potential, indicating a cross\u2010talk between lipid and ferro metabolic pathways. Mechanistically, glutathione peroxidase 4 (GPX4) interacts with SARS\u2010CoV\u20102 M, leading to its subsequent degradation by the Membrane Associated Ring\u2010CH\u2010Type Finger 1 (MARCHF1) ubiquitin ligase. M\u2010GPX4 interaction occurs at the R72 residue, which may represent a potential therapeutic target against SARS\u2010CoV\u20102 infection. M modulates lipid accumulation and further impairs mitochondrial functions, ultimately resulting in ferroptosis through MARCHF1\u2010GPX4 axis. Disrupting host\u2010virus interactions along this pathway may provide a therapeutic strategy for SARS\u2010CoV\u20102 infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jmv.70328","type":"journal-article","created":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T21:27:01Z","timestamp":1743888421000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["SARS\u2010CoV\u20102 Membrane Protein Induces MARCHF1\/GPX4\u2010Mediated Ferroptosis by Promoting Lipid Accumulation"],"prefix":"10.1002","volume":"97","author":[{"given":"Pei","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7996-1119","authenticated-orcid":false,"given":"Shuofeng","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Microbiology LKS Faculty of Medicine, The University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9182-1952","authenticated-orcid":false,"given":"Ye","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3964-5140","authenticated-orcid":false,"given":"Xing\u2010Yi","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-020-00459-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-0603-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48055-0"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.320518"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.02.013"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00689-x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01360-8"},{"issue":"2","key":"e_1_2_9_9_1","first-page":"51","article-title":"The Regulation of Iron Absorption and Homeostasis","volume":"37","author":"Wallace D. F.","year":"2016","journal-title":"Clinical Biochemist Reviews"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-22-3169"},{"issue":"3","key":"e_1_2_9_11_1","article-title":"Iron Overload and Hepcidin Overexpression Could Play a Key Role in Covid Infection, and May Explain Vulnerability in Elderly, Diabetics, and Obese Patients","volume":"91","author":"Banchini F.","year":"2020","journal-title":"Acta Bio\u2010Medica: Atenei Parmensis"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115637"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30490-6"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2021.12.006"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-023-01189-1"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009127"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2023.0750"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2023.03.008"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.01.030"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00735-4"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-019-0089-y"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2022.101198"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01839-8"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12551-023-01126-w"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-023-03476-6"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-01212-0"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2023.188890"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116512"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0699-0"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102752"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25021157"},{"key":"e_1_2_9_32_1","first-page":"123","article-title":"A SARS\u2010CoV\u20102\u2010human Protein\u2010Protein Interaction Map Reveals Drug Targets and Potential Drug\u2010Repurposing","volume":"2020","author":"O'Meara M. J.","year":"2020","journal-title":"BioRxiv"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05082-3"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-021-00338-2"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36432-0"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.10.042"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10030415"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaz055"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2024.2340399"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2023.108237"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29524-w"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32019-3"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-07143-z"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2024.05.066"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.70328","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T09:02:47Z","timestamp":1764666167000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.70328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/jmv.70328"],"URL":"https:\/\/doi.org\/10.1002\/jmv.70328","archive":["Portico"],"relation":{},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"value":"0146-6615","type":"print"},{"value":"1096-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2024-10-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70328"}}