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Cardiac involvement in DCMA ranges from mild conduction abnormalities to early severe myocardial dysfunction. Although evidence suggests that DCMA is linked to abnormalities in mitochondrial function, the molecular underpinnings of this condition are unclear, and there is no way to predict which patients will develop life\u2010threatening disease. To address this, we developed a metabolic flux assay for assessing the metabolic function of mitochondria in fibroblasts derived from DCMA patients. Using this approach, we discovered that DCMA fibroblasts have elevated glutamine uptake, increased glutamate and ammonium secretion, and elevated lactate production. Moreover, we observed that these cellular perturbations were closely correlated with cardiac dysfunction in a blinded cohort of patient cell lines. These findings suggest that glutamine catabolism is abnormal in DCMA and may serve as a predictor of clinical progression.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70018","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T18:34:32Z","timestamp":1741718072000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Altered Fibroblast Glutamine Metabolism Is Linked to the Severity of Cardiac Dysfunction in\n                    <scp>DCMA<\/scp>\n                    , a Mitochondrial Cardiomyopathy"],"prefix":"10.1002","volume":"48","author":[{"given":"Melissa A.","family":"King","sequence":"first","affiliation":[{"name":"Department of Biological Sciences University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine C.","family":"Heger","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Drikic","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayush","family":"Mandwal","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneal","family":"Khan","sequence":"additional","affiliation":[{"name":"M.A.G.I.C. 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Molecular Biology Cumming School of Medicine, University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian A.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.036657"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2012.92"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2016.03.020"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2016_23"},{"key":"e_1_2_11_6_1","first-page":"366","article-title":"Phenotype and Pathology of the Dilated Cardiomyopathy With Ataxia Syndrome in Children","volume":"1","author":"Machiraju P.","year":"2021","journal-title":"Journal of Inherited Metabolic Disease"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2019.09.021"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1047951107000042"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2018.02.019"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2019.00167"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.04.016"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000514"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac902837x"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac100565b"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrc.2526"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.06.043"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/1044-0305(94)80016-2"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.011"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq002"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2015.00003"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.738146"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.03.011"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.12.017"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac071583z"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22366"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2016-0190"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.03.002"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2016.00025"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs275"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T05:41:09Z","timestamp":1762839669000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.70018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/jimd.70018"],"URL":"https:\/\/doi.org\/10.1002\/jimd.70018","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"2024-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70018"}}