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Alongside MHC\u2010I overexpression, subtypes of myositis, display a distinct type I interferon (IFN) signature. This study examined the combinational effects of elevated MHC\u2010I and type I IFNs (IFN\u03b1\/\u03b2) on mitochondrial function, as mitochondrial dysfunction is often seen in IIMs. Human skeletal muscle myoblasts were transfected with an MHC\u2010I isoform using the mammalian HLA\u2010A2\/K\n                    <jats:sup>b<\/jats:sup>\n                    vector. Mitochondrial respiration, mitochondrial membrane potential, and reactive oxygen\/nitrogen species generation were assessed with or without IFN\u03b1 and IFN\u03b2. We show that MHC\u2010I overexpression in human skeletal muscle myoblasts led to decreased basal glycolysis and mitochondrial respiration, cellular spare respiratory capacity, adenosine triphosphate\u2010linked respiration, and an increased proton leak, which were all exaggerated by type I IFNs. Mitochondrial membrane depolarization was induced by MHC\u2010I overexpression both in absence and presence of type I IFNs. Human myoblasts overexpressing MHC\u2010I showed elevated nitric oxide generation that was abolished when combined with IFN. MHC\u2010I on its own did not result in an increased reactive oxygen species (ROS) production, but IFN on their own, or combined with MHC\u2010I overexpression did induce elevated ROS generation. Surprisingly, we observed no gross changes in mitochondrial reticular structure or markers of mitochondrial dynamics. We present new evidence that MHC\u2010I overexpression and type I IFNs aggravate the effects each has on mitochondrial function in human skeletal muscle cells, providing novel insights into their mechanisms of action and suggesting important implications in the further study of myositis pathogenesis.\n                  <\/jats:p>","DOI":"10.1002\/jcp.31458","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T06:50:02Z","timestamp":1728456602000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A combination of major histocompatibility complex (MHC) I overexpression and type I interferon induce mitochondrial dysfunction in human skeletal myoblasts"],"prefix":"10.1002","volume":"240","author":[{"given":"Anastasia","family":"Thoma","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Faculty of Science &amp; Engineering Manchester Metropolitan University Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razan","family":"Alomosh","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Faculty of Science &amp; Engineering Manchester Metropolitan University Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly L.","family":"Bond","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Faculty of Science &amp; Engineering Manchester Metropolitan University Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Akter\u2010Miah","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Faculty of Science &amp; Engineering Manchester Metropolitan University Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4215-2649","authenticated-orcid":false,"given":"Nasser","family":"Al\u2010Shanti","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Faculty of Science &amp; Engineering Manchester Metropolitan University Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Degens","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Faculty of Science &amp; Engineering Manchester Metropolitan University Manchester UK"},{"name":"Institute of Sport Science and Innovations Lithuanian Sports University Kaunas Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanja","family":"Pekovic\u2010Vaughan","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Faculty of Health and Life Science University of Liverpool Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1501-7879","authenticated-orcid":false,"given":"Adam P.","family":"Lightfoot","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Faculty of Science &amp; Engineering Manchester Metropolitan University Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"issue":"6","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s10735-004-2194-6","article-title":"Mitochondrial abnormalities in dermatomyositis: Characteristic pattern of neuropathology","volume":"35","author":"Alhatou M. 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