{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:35:23Z","timestamp":1791905723040,"version":"4.3.4"},"reference-count":62,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["12474435"],"award-info":[{"award-number":["12474435"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Skeletal muscle atrophy is tightly associated with maladaptive alterations in mitochondrial function and morphology. Itchy E3 ubiquitin\u2010protein ligase (ITCH) modulates mitochondria, and thrombospondin 1 (THBS1) positively regulates muscle atrophy, but their roles in muscle atrophy are unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A muscle atrophy model was established in C57BL\/6 mice via daily intraperitoneal injection of dexamethasone (Dex, 20\u2009mg\/kg). ITCH overexpression in skeletal muscle was achieved by adeno\u2010associated virus serotype 9 injection. C2C12 cells were treated with 50\u2009\u03bcM Dex to mimic in\u00a0vitro muscle atrophy. Skeletal muscle atrophy in mice was evaluated using hematoxylin\u2013eosin staining and immunofluorescence staining. Mitochondrial damage was assessed via transmission electron microscopy, succinate dehydrogenase staining, and JC\u20101 staining. Immunoprecipitation\u2010liquid chromatography\/mass spectrometry, molecular docking, and co\u2010immunoprecipitation were used to investigate the interaction between ITCH and THBS1. Phosphoproteomics analysis was performed to detect the THBS1 downstream proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Dex treatment downregulated ITCH expression in skeletal muscle. ITCH overexpression increased body weight, muscle mass, and muscle strength, downregulated the expression of atrophy\u2010related genes (Atrogin\u20101, Mstn, MuRF\u20101), and promoted mitochondrial biogenesis. The results of the C2C12 cells were consistent with those obtained in\u00a0vivo. Proteomic profiling and Co\u2010IP confirmed ITCH\u2013THBS1 interaction and subsequent THBS1 ubiquitination. THBS1 knockdown reduced the expression of Atrogin\u20101 and MuRF\u20101 and inhibited the phosphorylation of JUN and Map3k7, whereas THBS1 overexpression reversed the ITCH\u2010mediated improvement in mitochondrial biogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ITCH enhances mitochondrial biogenesis and mitigates Dex\u2010induced muscle atrophy by promoting the ubiquitin\u2010dependent degradation of THBS1 and subsequent inhibition of downstream JUN\/Map3k7 phosphorylation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.70299","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:28:27Z","timestamp":1787894907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>ITCH<\/scp>\n                    \u2010Mediated Ubiquitination and Degradation of\n                    <scp>THBS1<\/scp>\n                    : A Key Mechanism for Enhancing Mitochondrial Biogenesis and Alleviating Mouse Skeletal Muscle Atrophy"],"prefix":"10.1111","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2891-018X","authenticated-orcid":false,"given":"Wan","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Gerontology and Geriatrics Shengjing Hospital of China Medical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanteng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gerontology and Geriatrics Shengjing Hospital of China Medical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gerontology and Geriatrics Shengjing Hospital of China Medical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1118-658X","authenticated-orcid":false,"given":"Difei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gerontology and Geriatrics Shengjing Hospital of China Medical University  Shenyang 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