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Our previous study on the cardiotoxin mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from muscle disease patients, represented by dysferlinopathy (dysfy) (dystrophic pathology; n<\/jats:italic>\u00a0=\u00a043), polymyositis (PM<\/jats:styled-content>) (inflammatory pathology; n<\/jats:italic>\u00a0=\u00a024), and distal myopathy with rimmed vacuoles (DMRV<\/jats:styled-content>) (distal myopathy; n<\/jats:italic>\u00a0=\u00a031) were analyzed. Mitochondrial damage (ragged blue and COX<\/jats:styled-content>\u2010deficient fibers) was revealed in dysfy, PM<\/jats:styled-content>, and DMRV<\/jats:styled-content> cases by enzyme histochemistry (SDH<\/jats:styled-content> and COX<\/jats:styled-content>\u2010SDH<\/jats:styled-content>), electron microscopy (vacuolation and altered cristae) and biochemical assays (significantly increased ADP<\/jats:styled-content>\/ATP<\/jats:styled-content> ratio). Proteomic analysis of muscle mitochondria from all three muscle diseases by isobaric tag for relative and absolute quantitation labeling and liquid chromatography\u2010tandem mass spectrometry (LC<\/jats:styled-content>\u2010MS<\/jats:styled-content>\/MS<\/jats:styled-content>) analysis demonstrated down\u2010regulation of electron transport chain (ETC<\/jats:styled-content>) complex subunits, assembly factors and Krebs cycle enzymes. Interestingly, 80 of the under\u2010expressed proteins were common among the three pathologies. Assay of ETC<\/jats:styled-content> and Krebs cycle enzyme activities validated the MS<\/jats:styled-content> data. Mitochondrial proteins from muscle pathologies also displayed higher tryptophan (Trp) oxidation and the same was corroborated in the cardiotoxin model. Molecular modeling predicted Trp oxidation to alter the local structure of mitochondrial proteins. Our data highlight mitochondrial alterations in muscle pathologies, represented by morphological changes, altered mitochondrial proteome and protein oxidation, thereby establishing the role of mitochondrial damage in human muscle diseases.<\/jats:p><\/jats:sec>\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from dysferlinopathy (Dysfy), polymyositis (PM<\/jats:styled-content>), and distal myopathy with rimmed vacuoles (DMRV<\/jats:styled-content>) displayed morphological and biochemical evidences of mitochondrial dysfunction. Proteomic analysis revealed down\u2010regulation of electron transport chain (ETC<\/jats:styled-content>) subunits, assembly factors, and tricarboxylic acid (TCA<\/jats:styled-content>) cycle enzymes, with 80 proteins common among the three pathologies. Mitochondrial proteins from muscle pathologies also displayed higher Trp oxidation that could alter the local structure.<\/jats:p>Cover image for this issue: doi: 10.1111\/jnc.13324<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13626","type":"journal-article","created":{"date-parts":[[2016,3,26]],"date-time":"2016-03-26T16:58:21Z","timestamp":1459011501000},"page":"174-191","source":"Crossref","is-referenced-by-count":39,"title":["Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function"],"prefix":"10.1111","volume":"138","author":[{"given":"Balaraju","family":"Sunitha","sequence":"first","affiliation":[{"name":"Department of Neurochemistry National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Karnataka India"},{"name":"Department of Neuropathology National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narayanappa","family":"Gayathri","sequence":"additional","affiliation":[{"name":"Department of Neuropathology National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics Whitefield Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thottethodi Subrahmanya","family":"Keshava Prasad","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics Whitefield Bangalore Karnataka India"},{"name":"NIMHANS\u2010IOB Proteomics and Bioinformatics Laboratory Neurobiology Research Centre National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Karnataka India"},{"name":"YU\u2010IOB Center for Systems Biology and Molecular Medicine Yenepoya University Mangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atchayaram","family":"Nalini","sequence":"additional","affiliation":[{"name":"Department of Neurology National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balasundaram","family":"Padmanabhan","sequence":"additional","affiliation":[{"name":"Department of Biophysics National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muchukunte Mukunda","family":"Srinivas Bharath","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4565(02)00031-1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026952"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2808"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/1689"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.01009.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a011387"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(91)90546-6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.02.01302001a"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880100208"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.54.6.491"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf163"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00287.2002"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s100670200110"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1096\/fj.01-0685fje","article-title":"Differentiation\u2010specific alterations to glutathione synthesis in and hormonally stimulated release from human skeletal muscle cells","volume":"16","author":"Cotgreave I. 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