| http://purl.uniprot.org/citations/26345448 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26345448 | http://www.w3.org/2000/01/rdf-schema#comment | "Dysfunctions in mitochondrial complex I (NADH:ubiquinone oxidoreductase) are both genetically and clinically highly diverse and a major cause of human mitochondrial diseases. The genetic determinants of individual clinical cases are increasingly being described, but how these genetic defects affect complex I on the molecular and cellular level, and have different clinical consequences in different individuals, is little understood. Furthermore, without molecular-level information innocent genetic variants may be misassigned as pathogenic. Here, we have used a yeast model system (Yarrowia lipolytica) to study the molecular consequences of 16 single amino acid substitutions, classified as pathogenic, in the NDUFV1 subunit of complex I. NDUFV1 binds the flavin cofactor that oxidizes NADH and is the site of complex I-mediated reactive oxygen species production. Seven mutations caused loss of complex I expression, suggesting they are detrimental but precluding further study. In two variants complex I was fully assembled but did not contain any flavin, and four mutations led to functionally compromised enzymes. Our study provides a molecular rationale for assignment of all these variants as pathogenic. However, three variants provided complex I that was functionally equivalent to the wild-type enzyme, challenging their assignment as pathogenic. By combining structural, bioinformatic and functional data, a simple scoring system for the initial evaluation of future NDUFV1 variants is proposed. Overall, our results broaden understanding of how mutations in this centrally important core subunit of complex I affect its function and provide a basis for understanding the role of NDUFV1 mutations in mitochondrial dysfunction."xsd:string |
| http://purl.uniprot.org/citations/26345448 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddv344"xsd:string |
| http://purl.uniprot.org/citations/26345448 | http://purl.uniprot.org/core/author | "Hirst J."xsd:string |
| http://purl.uniprot.org/citations/26345448 | http://purl.uniprot.org/core/author | "Bridges H.R."xsd:string |
| http://purl.uniprot.org/citations/26345448 | http://purl.uniprot.org/core/author | "Varghese F."xsd:string |
| http://purl.uniprot.org/citations/26345448 | http://purl.uniprot.org/core/author | "Atcheson E."xsd:string |
| http://purl.uniprot.org/citations/26345448 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26345448 | http://purl.uniprot.org/core/name | "Hum Mol Genet"xsd:string |
| http://purl.uniprot.org/citations/26345448 | http://purl.uniprot.org/core/pages | "6350-6360"xsd:string |
| http://purl.uniprot.org/citations/26345448 | http://purl.uniprot.org/core/title | "Characterization of clinically identified mutations in NDUFV1, the flavin-binding subunit of respiratory complex I, using a yeast model system."xsd:string |
| http://purl.uniprot.org/citations/26345448 | http://purl.uniprot.org/core/volume | "24"xsd:string |
| http://purl.uniprot.org/citations/26345448 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26345448 |
| http://purl.uniprot.org/citations/26345448 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/26345448 |
| http://purl.uniprot.org/uniprot/#_B4DUN7-mappedCitation-26345448 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26345448 |
| http://purl.uniprot.org/uniprot/#_B4DE93-mappedCitation-26345448 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26345448 |
| http://purl.uniprot.org/uniprot/#_G3V0I5-mappedCitation-26345448 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26345448 |
| http://purl.uniprot.org/uniprot/#_E5KNH5-mappedCitation-26345448 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26345448 |
| http://purl.uniprot.org/uniprot/#_P49821-mappedCitation-26345448 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26345448 |
| http://purl.uniprot.org/uniprot/#_Q53G70-mappedCitation-26345448 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26345448 |
| http://purl.uniprot.org/uniprot/#_Q96ID4-mappedCitation-26345448 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26345448 |
| http://purl.uniprot.org/uniprot/P49821 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/26345448 |
| http://purl.uniprot.org/uniprot/G3V0I5 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/26345448 |
| http://purl.uniprot.org/uniprot/Q53G70 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/26345448 |
| http://purl.uniprot.org/uniprot/E5KNH5 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/26345448 |