{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T04:03:02Z","timestamp":1771905782223,"version":"3.50.1"},"posted":{"date-parts":[[2026,2,20]]},"group-title":"Neuroscience","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"name":"National Institute of Arthritis, Musculoskeletal and Skins Diseases","award":["K08-AR78254"],"award-info":[{"award-number":["K08-AR78254"]}]},{"DOI":"10.13039\/100025799","name":"American Neuromuscular Foundation","doi-asserted-by":"crossref","award":["career development grant"],"award-info":[{"award-number":["career development grant"]}],"id":[{"id":"10.13039\/100025799","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Mayo Clinic Center for Clinical and Translational Sciences","award":["UL1TR002377"],"award-info":[{"award-number":["UL1TR002377"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AG 55549-9"],"award-info":[{"award-number":["R01AG 55549-9"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["RF1NS085070"],"award-info":[{"award-number":["RF1NS085070"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Oxidative phosphorylation (OXPHOS) is a central function and a key indicator of mitochondrial fitness, yet studies in human tissue remain limited. Inclusion body myositis (IBM) is a progressive myopathy that lies at the intersection of aging, inflammation and mitochondrial dysfunction. We aimed to perform a comprehensive profiling of mitochondrial respiration in muscle tissue from patients with IBM.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A wide battery of complementary tests from RNA level to high-resolution respirometry on permeabilized muscle fibers was performed. The relationship between respiration, mitochondrial content, mitochondrial DNA (mtDNA) abnormalities and mitophagy was examined, along with the correlation with various clinical parameters to determine the clinical significance of the findings.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    The study included a total of 67 patients with IBM and 45 controls. IBM muscle tissue exhibited reduced maximal respiration per tissue weight in State 3 (high substrates, high ADP) and uncoupled state with decreased coupling efficiency and higher leak control ratios. When adjusting for citrate synthase reflecting mitochondrial content, males had decreased State 3 intrinsic respiration, whereas females had greater intrinsic respiration in leak states. Complex II control ratio strongly correlated with disease duration and severity only in females. IBM was associated with decreased RNA and protein expression of OXPHOS complexes. Complex I activity was decreased mainly in females. IBM samples exhibited lower maximal H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    emission, accompanied by a higher total antioxidant capacity that correlated with disease duration in females. In IBM, there was decreased mtDNA content, and impaired mitophagy, both of which strongly correlated with respirometry measures and markers of disease severity, indicating these pathways are likely interconnected and of clinical significance.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>IBM is characterized by multilevel impairments in mitochondrial coupling efficiency, revealing several potential therapeutic targets to improve mitochondrial fitness, while accounting for sex-specific differences.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.18.706692","type":"posted-content","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T16:35:23Z","timestamp":1771605323000},"source":"Crossref","is-referenced-by-count":0,"title":["Multilevel impairment of mitochondrial respiration with sex-specific signatures in inclusion body myositis"],"prefix":"10.64898","author":[{"given":"Ibrahim","family":"Shammas","sequence":"first","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hazem","family":"Iaali","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens O.","family":"Watzlawik","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noemi Vidal","family":"Folch","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surendra","family":"Dasari","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graeme","family":"Preston","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA"},{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thi Kim","family":"Oanh Nguyen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfdieter","family":"Springer","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamas","family":"Kozicz","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA"},{"name":"Department of Genetics and Genomic 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