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Congenital muscular dystrophy type 1A (MDC1A) is a severe muscle disorder caused by mutations in the\n                    <jats:italic>LAMA2<\/jats:italic>\n                    gene. Leigh syndrome (LS) is a neurometabolic disease caused by mutations in genes related to mitochondrial function. Skeletal muscle is severely affected in both diseases and a common feature is muscle weakness that leads to hypotonia and respiratory problems. Here, we have investigated the bioenergetic profile in myogenic cells from MDC1A and LS patients. We found dysregulated expression of genes related to energy production, apoptosis and proteasome in myoblasts and myotubes. Moreover, impaired mitochondrial function and a compensatory upregulation of glycolysis were observed when monitored in real-time. Also, alterations in cell cycle populations in myoblasts and enhanced caspase-3 activity in myotubes were observed. Thus, we have for the first time demonstrated an impairment of the bioenergetic status in human MDC1A and LS muscle cells, which could contribute to cell cycle disturbance and increased apoptosis. Our findings suggest that skeletal muscle metabolism might be a promising pharmacological target in order to improve muscle function, energy efficiency and tissue maintenance of MDC1A and LS patients.\n                  <\/jats:p>","DOI":"10.1038\/srep45272","type":"journal-article","created":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T06:03:52Z","timestamp":1491199432000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Bioenergetic Impairment in Congenital Muscular Dystrophy Type 1A and Leigh Syndrome Muscle Cells"],"prefix":"10.1038","volume":"7","author":[{"given":"Cibely C.","family":"Fontes-Oliveira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Steinz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Schneiderat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hindrik","family":"Mulder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Durbeej","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,3]]},"reference":[{"key":"BFsrep45272_CR1","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/nrm.2016.7","volume":"17","author":"AE Almada","year":"2016","unstructured":"Almada, A. E. & Wagers, A. J. Molecular circuitry of stem cell fate in skeletal muscle regeneration, ageing and disease. Nature reviews. Molecular cell biology 17, 267\u2013279, doi: 10.1038\/nrm.2016.7 (2016).","journal-title":"Nature reviews. Molecular cell biology"},{"key":"BFsrep45272_CR2","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1111\/j.1365-201X.2004.01372.x","volume":"182","author":"DJ Marcinek","year":"2004","unstructured":"Marcinek, D. J. Mitochondrial dysfunction measured in vivo . Acta physiologica Scandinavica 182, 343\u2013352, doi: 10.1111\/j.1365-201X.2004.01372.x (2004).","journal-title":"Acta physiologica Scandinavica"},{"key":"BFsrep45272_CR3","doi-asserted-by":"publisher","first-page":"32","DOI":"10.3389\/fphys.2014.00032","volume":"5","author":"R Koopman","year":"2014","unstructured":"Koopman, R., Ly, C. H. & Ryall, J. G. A metabolic link to skeletal muscle wasting and regeneration. 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