{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T15:40:20Z","timestamp":1776440420554,"version":"3.51.2"},"reference-count":24,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"fondecyt","award":["1200255"],"award-info":[{"award-number":["1200255"]}]},{"DOI":"10.13039\/501100018735","name":"fondap","doi-asserted-by":"crossref","award":["15150012"],"award-info":[{"award-number":["15150012"]}],"id":[{"id":"10.13039\/501100018735","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Idiopathic Inflammatory Myopathies (IIMs) have been studied within the framework of autoimmune diseases where skeletal muscle appears to have a passive role in the illness. However, persiting weakness even after resolving inflammation raises questions about the role that skeletal muscle plays by itself in these diseases. \"Non-immune mediated\" hypotheses have arisen to consider inner skeletal muscle cell processes as trigger factors in the clinical manifestations of IIMs. Alterations in oxidative phosphorylation, ATP production, calcium handling, autophagy, endoplasmic reticulum stress, among others, have been proposed as alternative cellular pathophysiological mechanisms. In this study, we used skeletal muscle-derived cells, from healthy controls and IIM patients to determine mitochondrial function and mitochondrial ability to adapt to a metabolic stress when deprived of glucose. We hypothesized that mitochondria would be dysfunctional in IIM samples, which was partially true in normal glucose rich growing medium as determined by oxygen consumption rate. However, in the glucose-free and galactose supplemented condition, a medium that forced mitochondria to function, IIM cells increased their respiration, reaching values matching normal derived cells. Unexpectedly, cell death significantly increased in IIM cells under this condition. Our findings show that mitochondria in IIM is functional and the decrease respiration observed is part of an adaptative response to improve survival. The increased metabolic function obtained after forcing IIM cells to rely on mitochondrial synthesized ATP is detrimental to the cell\u2019s viability. Thus, therapeutic interventions that activate mitochondria, could be detrimental in IIM cell physiology, and must be avoided in patients with IIM.<\/jats:p>","DOI":"10.1371\/journal.pone.0242443","type":"journal-article","created":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T18:46:38Z","timestamp":1605897998000},"page":"e0242443","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Idiopathic inflammatory myopathy human derived cells retain their ability to increase mitochondrial function"],"prefix":"10.1371","volume":"15","author":[{"given":"Carla","family":"Basualto-Alarc\u00f3n","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F\u00e9lix A.","family":"Urra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Francisca","family":"Boz\u00e1n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7786-4569","authenticated-orcid":true,"given":"Fabi\u00e1n","family":"Ja\u00f1a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandra","family":"Trangulao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0525-9308","authenticated-orcid":true,"given":"Jorge A.","family":"Bevilacqua","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1115-2790","authenticated-orcid":true,"given":"J. C\u00e9sar","family":"C\u00e1rdenas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,11,20]]},"reference":[{"issue":"5","key":"pone.0242443.ref001","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrrheum.2018.41","article-title":"Classification of myositis","volume":"14","author":"IE Lundberg","year":"2018","journal-title":"Nat Rev Rheumatol"},{"issue":"1","key":"pone.0242443.ref002","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/2044-5040-3-13","article-title":"Idiopathic inflammatory myopathies: pathogenic mechanisms of muscle weakness","volume":"3","author":"S Rayavarapu","year":"2013","journal-title":"Skeletal muscle"},{"issue":"6","key":"pone.0242443.ref003","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1002\/art.21103","article-title":"Activation of the endoplasmic reticulum stress response in autoimmune myositis: potential role in muscle fiber damage and dysfunction","volume":"52","author":"K Nagaraju","year":"2005","journal-title":"Arthritis rheum"},{"issue":"209","key":"pone.0242443.ref004","article-title":"Role of non-immune mechanisms of muscle damage in idiopathic inflammatory myopathies","volume":"14","author":"W Coley","year":"2012","journal-title":"Arthritis Res Ther"},{"issue":"12","key":"pone.0242443.ref005","doi-asserted-by":"crossref","first-page":"3248","DOI":"10.1002\/art.38180","article-title":"Activation of the ubiquitin proteasome pathway in a mouse model of inflammatory myopathy: a potential therapeutic target","volume":"65","author":"S Rayavarapu","year":"2013","journal-title":"Arthritis Rheum"},{"issue":"5","key":"pone.0242443.ref006","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1007\/s004010050462","article-title":"Cytochrome c oxidase deficiencies in the muscle of patients with inflammatory myopathies","volume":"91","author":"P Chariot","year":"1996","journal-title":"Acta neuropathol"},{"issue":"6","key":"pone.0242443.ref007","first-page":"615","article-title":"Mitochondrial abnormalities in dermatomyositis: characteristic pattern of neuropathology","volume":"35","author":"MI Alhatou","year":"2004","journal-title":"J Mol Histol"},{"issue":"6","key":"pone.0242443.ref008","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1136\/ard.54.6.491","article-title":"Cabello a, Gomez-Reino JJ. Respiratory chain enzyme defects in patients with idiopathic inflammatory myopathy","volume":"54","author":"Y Campos","year":"1995","journal-title":"Ann Rheum Dis"},{"issue":"5","key":"pone.0242443.ref009","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1002\/art.1780370519","article-title":"Magnetic resonance imaging and P-31 magnetic resonance spectroscopy provide unique quantitative data useful in the longitudinal management of patients with dermatomyositis","volume":"37","author":"JH Park","year":"1994","journal-title":"Arthritis Rheum"},{"issue":"11","key":"pone.0242443.ref010","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1002\/(SICI)1097-4598(199811)21:11<1523::AID-MUS22>3.0.CO;2-#","article-title":"Intracellular phosphates in inclusion body myositis\u2014a 31P magnetic resonance spectroscopy study","volume":"21","author":"Z Argov","year":"1998","journal-title":"Muscle & nerve"},{"issue":"Pt 7","key":"pone.0242443.ref011","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1093\/brain\/awf163","article-title":"Reduced oxidative phosphorylation and proton efflux suggest reduced capillary blood supply in skeletal muscle of patients with dermatomyositis and polymyositis: a quantitative 31P-magnetic resonance spectroscopy and MRI study","volume":"125","author":"G Cea","year":"2002","journal-title":"Brain: a journal of neurology"},{"issue":"2","key":"pone.0242443.ref012","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/art.1780350212","article-title":"P31 magnetic resonance spectroscopy in polymositis and dermatomyositis: altered energy utilization during exercise","volume":"35","author":"ED Newman","year":"1992","journal-title":"Arthritis and rheumatism"},{"issue":"6","key":"pone.0242443.ref013","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1093\/rheumatology\/keh182","article-title":"Metabolic disturbances during short exercises in dermatomyositis revealed by real-time functional 31P magnetic resonance spectroscopy","volume":"43","author":"B Pfleiderer","year":"2004","journal-title":"Rheumatology"},{"issue":"7","key":"pone.0242443.ref014","doi-asserted-by":"crossref","DOI":"10.1007\/s11926-014-0429-4","article-title":"New insights into the benefits of exercise for muscle health in patients with idiopathic inflammatory myositis","volume":"16","author":"L Alemo Munters","year":"2014","journal-title":"Curr Rheumatol Rep"},{"issue":"12","key":"pone.0242443.ref015","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0028536","article-title":"Galactose enhances oxidative metabolism and reveals mitochondrial dysfunction in human primary muscle cells","volume":"6","author":"C Aguer","year":"2011","journal-title":"PLoS ONE"},{"issue":"8","key":"pone.0242443.ref016","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1371\/journal.pone.0070772","article-title":"Low Glucose but Not Galactose Enhances Oxidative Mitochondrial Metabolism in C2C12 Myoblasts and Myotubes","volume":"8","author":"M Elkalaf","year":"2013","journal-title":"PLoS ONE"},{"issue":"4","key":"pone.0242443.ref017","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s00401-017-1731-9","article-title":"IFN-\u03b2-induced reactive oxygen species and mitochondrial damage contribute to muscle impairment and inflammation maintenance in dermatomyositis","volume":"134","author":"A Meyer","year":"2017","journal-title":"Acta Neuropathol"},{"issue":"7","key":"pone.0242443.ref018","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1136\/annrheumdis-2014-207172","article-title":"In the idiopathic inflammatory myopathies (IIM), do reactive oxygen species (ROS) contribute to muscle weakness?","volume":"74","author":"AP Lightfoot","year":"2015","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"pone.0242443.ref019","first-page":"51","article-title":"Hydrophobic acridine dyes for fluorescent staining of mitochondria in living cells. 3. Specific accumulation of the fluorescent dye NAO on the mitochondrial membranes in HeLa cells by hydrophobic interaction. Depression of respiratory activity, changes in the ultrastructure of mitochondria due to NAO. Increase of fluorescence in vital stained mitochondria in situ by irradiation","volume":"82","author":"M Septinus","year":"1985","journal-title":"Histochemistry"},{"issue":"3","key":"pone.0242443.ref020","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/(SICI)1097-0320(20000301)39:3<203::AID-CYTO5>3.0.CO;2-Z","article-title":"Staining of mitochondrial membranes with 10-nonyl acridine orange, MitoFluor Green, and MitoTracker Green is affected by mitochondrial membrane potential altering drugs","volume":"39","author":"JF Keij","year":"2000","journal-title":"Cytometry"},{"issue":"2","key":"pone.0242443.ref021","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1046\/j.1471-4159.2002.00945.x","article-title":"Intracellular distribution of the fluorescent dye nonyl acridine orange responds to the mitochondrial membrane potential: implications for assays of cardiolipin and mitochondrial mass","volume":"82","author":"J Jacobson","year":"2002","journal-title":"J Neurochem"},{"issue":"3","key":"pone.0242443.ref022","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1006\/clin.1998.4527","article-title":"Cell death and Oxidative damage in Inflammatory Myopathies","volume":"87","author":"DS Tews","year":"1998","journal-title":"Clin Immunol Immunopathol"},{"issue":"2","key":"pone.0242443.ref023","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/0885-4505(92)90056-5","article-title":"Nonviability of cells with oxidative defects in galactose medium: A screening test for affected patient fibroblasts","volume":"48","author":"BH Robinson","year":"1992","journal-title":"Biochem Med Metab Biol"},{"issue":"1","key":"pone.0242443.ref024","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.redox.2013.12.028","article-title":"Modulation of mitochondrial bioenergetics in a skeletal muscle cell line model of mitochondrial toxicity","volume":"2","author":"W Dott","year":"2014","journal-title":"Redox Biol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0242443","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T18:46:56Z","timestamp":1605898016000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0242443"}},"subtitle":[],"editor":[{"given":"Jianhua","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2020,11,20]]},"references-count":24,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0242443","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,20]]}}}