{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T22:55:30Z","timestamp":1772578530421,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Caribbean Society of Myology, the French National Institute for Scientific and Medical Research (INSERM)"},{"name":"University of Bordeaux"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acyl-CoA dehydrogenase 9 deficiency is considered as a rare neuromuscular syndrome with an autosomal recessive transmission. The ACAD9 protein presents two essential functions, i.e., the limiting step enzyme of the fatty acid \u03b2-oxidation pathway and one of the complex\u2019s compounds involved in the respiratory chain complex I assembly. Thus, loss-of-function mutations are known to convey mitochondrial cytopathologies. A patient with a mild and late-onset phenotype, suffering from exercise intolerance and hypertrophic cardiomyopathy, was diagnosed as a compound heterozygote of the ACAD9 gene. The first c.1240C&gt; T p.Arg414Cys variant has been previously reported and is known to be responsible for ACAD9 deficiency. However, the second c.1636G&gt; A p.Val546Met variant has never been described. The goal was to investigate the eventual pathogenicity of this new genetic variant. For this purpose, molecular cloning was generated to express the ACAD9 gene with the V546M variant in a cell line (ACAD9mut) and compared to cells expressing the wild-type ACAD9. Then, the mitochondrial respiration, ATP production, the mitochondrial network, and the oxidative phosphorylation\u2019s composition were investigated to reveal the effects of the V546M variant. While avoiding to affect the amount of the respiratory chain\u2019s complexes, the new ACAD9 variant was entirely responsible for reducing over 50% of the mitochondrial complex I activity.<\/jats:p>","DOI":"10.3390\/ijms26157128","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T07:54:26Z","timestamp":1753343666000},"page":"7128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Late-Onset and Mild Phenotype of Mitochondrial Complex I Deficiency Due to a Novel Reported Variant Within the ACAD9 Gene"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2260-2021","authenticated-orcid":false,"given":"Anna Gaelle","family":"Giguet-Valard","sequence":"first","affiliation":[{"name":"Department of Rare Neurological and Neuromuscular Diseases\u2014Martinique University Hospital, 97261 Fort-de-France, Martinique, France"},{"name":"BIOSPHERES\u2014AREBio Laboratory, 97233 Schoelcher, Martinique, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7204-7826","authenticated-orcid":false,"given":"Samira","family":"Ait-El-Mkadem Saadi","sequence":"additional","affiliation":[{"name":"Genetics Laboratory Department Mitochondrial Pathologies, University Hospital Center of Nice, 06000 Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Duclos","sequence":"additional","affiliation":[{"name":"Department of Rare Neurological and Neuromuscular Diseases\u2014Martinique University Hospital, 97261 Fort-de-France, Martinique, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didier","family":"Lacombe","sequence":"additional","affiliation":[{"name":"INSERM U1211, Rare Diseases: Genetics and Metabolism, 33076 Bordeaux, France"},{"name":"Biological and Medical Sciences Research Department, University of Bordeaux, 33076 Bordeaux, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6093-0838","authenticated-orcid":false,"given":"R\u00e9mi","family":"Bellance","sequence":"additional","affiliation":[{"name":"Department of Rare Neurological and Neuromuscular Diseases\u2014Martinique University Hospital, 97261 Fort-de-France, Martinique, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nad\u00e8ge","family":"Bellance","sequence":"additional","affiliation":[{"name":"INSERM U1211, Rare Diseases: Genetics and Metabolism, 33076 Bordeaux, France"},{"name":"Biological and Medical Sciences Research Department, University of Bordeaux, 33076 Bordeaux, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1093\/brain\/awq273","article-title":"Riboflavin-responsive oxidative phosphorylation complex I deficiency caused by defective ACAD9: New function for an old gene","volume":"134","author":"Gerards","year":"2011","journal-title":"Brain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1086\/519219","article-title":"A new genetic disorder in mitochondrial fatty acid beta-oxidation: ACAD9 deficiency","volume":"81","author":"He","year":"2007","journal-title":"Am. 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