{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:34:30Z","timestamp":1791333270213,"version":"4.3.1"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,11,22]],"date-time":"2012-11-22T00:00:00Z","timestamp":1353542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cofactor disorders of mitochondrial energy metabolism are a heterogeneous group of diseases with a wide variety of clinical symptoms, particular metabolic profiles and variable enzymatic defects. Mutations in <jats:italic>NFU1<\/jats:italic> were recently identified in patients with fatal encephalopathy displaying a biochemical phenotype consistent with defects in lipoic acid\u2010dependent enzymatic activities and respiratory chain complexes. This discovery highlighted the molecular function of NFU1 as an iron\u2010sulfur(Fe\u2010S) cluster protein necessary for lipoic acid biosynthesis and respiratory chain complexes activities. To understand the pathophysiological mechanisms underlying this disease we have characterized the protein expression profiles of patients carrying <jats:italic>NFU1<\/jats:italic> mutations. Fibroblasts from patients with the p.Gly208Cys mutation showed complete absence of protein\u2010bound lipoic acid and decreased SDHA and SDHB subunits of complex II. In contrast, subunits of other respiratory chain complexes were normal. Protein lipoylation was also decreased in muscle and liver but not in other tissues available (brain, kidney, lung) from NFU1 patients. Although levels of the respiratory chain subunits were unaltered in tissues, BN\u2010PAGE showed an assembly defect for complex II in muscle, consistent with the low enzymatic activity of this complex. This study provides new insights into the molecular bases of NFU1 disease as well as into the regulation of NFU1 protein in human tissues. We demonstrate a ubiquitous expression of NFU1 protein and further suggest that defects in lipoic acid biosynthesis and complex II are the main molecular signature of this disease, particularly in patients carrying the p.Gly208Cys mutation.<\/jats:p>","DOI":"10.1007\/s10545-012-9565-z","type":"journal-article","created":{"date-parts":[[2012,11,22]],"date-time":"2012-11-22T19:26:00Z","timestamp":1353612360000},"page":"841-847","source":"Crossref","is-referenced-by-count":33,"title":["Protein expression profiles in patients carrying <i>NFU1<\/i> mutations. Contribution to the pathophysiology of the disease"],"prefix":"10.1002","volume":"36","author":[{"given":"X\u00e8nia","family":"Ferrer\u2010Cort\u00e8s","sequence":"first","affiliation":[{"name":"Secci\u00f3 d'Errors Cong\u00e8nits del Metabolisme, Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular, Hospital Clinic, IDIBAPS Barcelona 08028 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Font","sequence":"additional","affiliation":[{"name":"Secci\u00f3 d'Errors Cong\u00e8nits del Metabolisme, Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular, Hospital Clinic, IDIBAPS Barcelona 08028 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00faria","family":"Bujan","sequence":"additional","affiliation":[{"name":"Secci\u00f3 d'Errors Cong\u00e8nits del Metabolisme, Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular, Hospital Clinic, IDIBAPS Barcelona 08028 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