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RNA sequencing, immunoblotting, transmission electron microscopy, MRI, NMR, histochemical and mitochondrial function assays were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Loss of <jats:italic>Tieg1<\/jats:italic> expression resulted in altered sarcomere organization and a significant decrease in mitochondrial number. Histochemical analyses demonstrated an absence of succinate dehydrogenase staining and a decrease in cytochrome c oxidase (COX) enzyme activity in KO soleus with similar, but diminished, effects in the EDL. Decreased complex I, COX and citrate synthase (CS) activities were detected in the soleus muscle of KO mice indicating altered mitochondrial function. Complex I activity was also diminished in KO EDL. Significant decreases in CS and respiratory chain complex activities were identified in KO soleus. <jats:sup>1<\/jats:sup>H\u2010NMR spectra revealed no significant metabolic difference between wild\u2010type and KO muscles. However, <jats:sup>31<\/jats:sup>P spectra revealed a significant decrease in phosphocreatine and ATP\u03b3. Altered expression of 279 genes, many of which play roles in mitochondrial and muscle function, were identified in KO soleus muscle. Ultimately, all of these changes resulted in an exercise intolerance phenotype in <jats:italic>Tieg1<\/jats:italic> KO mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings have implicated novel roles for <jats:italic>Tieg1<\/jats:italic> in muscle including regulation of gene expression, metabolic activity and organization of tissue ultrastructure. This muscle phenotype resembles diseases associated with exercise intolerance and myopathies of unknown consequence.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13394","type":"journal-article","created":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T10:37:07Z","timestamp":1569580627000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Novel role of <i>Tieg1<\/i> in muscle metabolism and mitochondrial oxidative capacities"],"prefix":"10.1111","volume":"228","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6355-1713","authenticated-orcid":false,"given":"Malek","family":"Kammoun","sequence":"first","affiliation":[{"name":"Biomechanics and Bioengineering Laboratory Alliance Sorbonne Universit\u00e9s Universit\u00e9 de Technologie de Compi\u00e8gne UMR CNRS 7338 Compi\u00e8gne 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