{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:29:50Z","timestamp":1787765390217,"version":"build-2784847793"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"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":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Skeletal muscle wasting and weakness are prominent disease features. Originally considered to arise from common transcriptional changes, recent analyses demonstrated that different stimuli induce muscle wasting via largely distinct mRNA and protein changes.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Here, we examined the post\u2010translational modifications (PTMs) associated with muscle wasting induced by cancer (\n n<\/jats:italic>\n \u2009=\u200915\u2009078), dexamethasone (\n n\u2009=<\/jats:italic>\n \u200915\u2009078) and aging (\n n<\/jats:italic>\n \u2009=\u20098777) in mice by utilising the JUMPptm pipeline to recover modified peptides from TMT (tandem mass tag) mass spectrometry analyses.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We find that most PTMs that are significantly regulated are stimulus\u2010specific and that only a few are cross\u2010shared (\n n<\/jats:italic>\n \u2009=\u200910;\n p<\/jats:italic>\n \u2009<\u20090.05). These include P27 dihydroxylation of Lrpprc (leucine\u2010rich pentatricopeptide repeat containing), an RNA binding protein and transcriptional co\u2010activator mutated in Leigh syndrome, a mitochondrial disease. Contrary to the stimulus\u2010specificity of other atrophy\u2010associated PTMs, P27 dihydroxylation of Lrpprc declines (~20%;\n p<\/jats:italic>\n \u2009<\u20090.05) with muscle wasting irrespective of the atrophic trigger. Electroporation of dihydroxylation\u2010resistant Lrpprc\n P27A<\/jats:sup>\n (which mimics the reduction in Lrpprc dihydroxylation that occurs with atrophy) reduces muscle force in young (~23%\u201339%;\n p<\/jats:italic>\n \u2009<\u20090.01) and old (~26%\u201336%;\n p<\/jats:italic>\n \u2009<\u20090.01) male mice compared to the contralateral electroporation of Lrpprc\n WT<\/jats:sup>\n , indicating that a decline in Lrpprc P27 dihydroxylation contributes to muscle weakness in response to diverse catabolic stimuli. Comparison of Lrpprc\n WT<\/jats:sup>\n versus GFP electroporation indicates that there are mostly non\u2010significant effects (\n p<\/jats:italic>\n \u2009>\u20090.05) on muscle force in young and old mice. Mechanistically, Lrpprc\n P27A<\/jats:sup>\n does not affect proteostasis and mitochondrial function compared to control Lrpprc\n WT<\/jats:sup>\n but impairs (>\u200960% decline;\n p<\/jats:italic>\n \u2009<\u20090.05) the expression of genes necessary for muscle strength, including the apelin receptor\n Aplnr<\/jats:italic>\n and\n Col6a2\/6<\/jats:italic>\n collagens. Moreover, Lrpprc\n P27A<\/jats:sup>\n reduces type 2b myofibre size (13% decline;\n p<\/jats:italic>\n \u2009<\u20090.01) in old but not in young age.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These analyses identify atrophy\u2010associated PTMs that provide refined biomarkers for fingerprinting the atrophic stimulus. Although most PTMs are stimulus\u2010specific, P27 dihydroxylation of Lrpprc declines during muscle wasting induced by cancer, dexamethasone and aging, suggesting that this is a general atrophy marker. Experimental up\u2010regulation of the atrophy\u2010mimicking variant Lrpprc\n P27A<\/jats:sup>\n reduces muscle force compared to wild\u2010type Lrpprc in young and old mice, suggesting that atrophy\u2010associated P27 dihydroxylation contributes to disease\u2010associated muscle weakness.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70220","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T01:51:47Z","timestamp":1770256307000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Largely Distinct Post\u2010Translational Modifications Differentiate Skeletal Muscle Wasting Caused by Cancer, Dexamethasone and Aging"],"prefix":"10.1002","volume":"17","author":[{"given":"Anna","family":"Stephan","sequence":"first","affiliation":[{"name":"Department of Developmental Neurobiology St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia\u00a0A.","family":"Graca","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurobiology St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Poudel","sequence":"additional","affiliation":[{"name":"Department of Immunology St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxue","family":"Fu","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Labelle","sequence":"additional","affiliation":[{"name":"Division of Molecular Oncology, Department of Oncology St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8698-9555","authenticated-orcid":false,"given":"Fabio","family":"Demontis","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurobiology St. Jude Children's Research Hospital Memphis Tennessee 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