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Functional deficits often exceed the loss in muscle mass and myosin content. However, the mechanisms underlying the loss of force and emergence of myosin\u2010expressing non\u2010force\u2010generating fibers remain elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Myosin dysfunction was investigated in six intensive care unit patients exposed to a 12\u2010day mechanical ventilation and immobilization period using mass spectrometry\u2010based proteomics and molecular dynamics simulations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Previous single muscle fiber analyses revealed decreased fiber size and specific force from the 1st to the 12th days in all patients. A subset of myosin\u2010expressing fibers exhibiting a complete loss of contractile function was identified in three of the patients despite similar atrophy levels (~30%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) after 12\u2009days. All fibers had decreased specific force after 12\u2009days of mechanical ventilation, but 9% to 21% of the fibers were non\u2010force generating. The decline in specific force was linked to 27 post\u2010translational myosin modifications, including oxidation, ubiquitination, acetylation, and methylation. Molecular dynamics simulations indicated oxidation\u2010induced rigidity of the myosin head, predicted to compromise the flexibility of the actin\u2010binding and converter domains. Non\u2010force\u2010generating fibers exhibited a unique proteomic signature predicted to enhance myosin motor domain exposure and rigidity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In addition to muscle wasting and myosin loss, abnormal myosin post\u2010translational modifications contribute to muscle weakness in ICU patients with CIM, including the development of muscle fibers incapable of generating contractile force.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.70240","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T04:13:52Z","timestamp":1781842432000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Myosin Post\u2010Translational Modifications Associated With Critical Illness Myopathy"],"prefix":"10.1111","volume":"242","author":[{"given":"Fernando","family":"Ribeiro","sequence":"first","affiliation":[{"name":"Center for Molecular Medicine (CMM) Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Anatomy, Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1822-7142","authenticated-orcid":false,"given":"Bruno","family":"Di Geronimo","sequence":"additional","affiliation":[{"name":"School of Chemistry and Biochemistry Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Cacciani","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine (CMM) Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Clinical Sciences, Comparative Medicine Swedish University of Agricultural Sciences  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Widgren","sequence":"additional","affiliation":[{"name":"Analytical Chemistry and Neurochemistry, Department of Chemistry for Life Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvette","family":"Hedstr\u00f6m","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine (CMM) Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Clinical Sciences, Comparative Medicine Swedish University of Agricultural Sciences  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anselmo S.","family":"Moriscot","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Kasson","sequence":"additional","affiliation":[{"name":"School of Chemistry and Biochemistry Georgia Institute of Technology  Atlanta Georgia USA"},{"name":"Department of Cell and Molecular Biology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shina C. 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