| http://purl.uniprot.org/citations/32668765 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32668765 | http://www.w3.org/2000/01/rdf-schema#comment | "KMT2D encodes a methyltransferase responsible for histone 3 lysine 4 (H3K4) mono-/di-methylation, an epigenetic mark correlated with active transcription. Here, we tested the hypothesis that KMT2D pathogenic loss-of-function variants, which causes the Kabuki syndrome type 1, could affect the mitochondrial metabolic profile. By using Seahorse technology, we showed a significant reduction of the mitochondrial oxygen consumption rate as well as a reduction of the glycolytic flux in both Kmt2d knockout MEFs and skin fibroblasts of Kabuki patients harboring heterozygous KMT2D pathogenic variants. Mass-spectrometry analysis of intermediate metabolites confirmed alterations in the glycolytic and TCA cycle pathways. The observed metabolic phenotype was accompanied by a significant increase in the production of reactive oxygen species. Measurements of the specific activities of the mitochondrial respiratory chain complexes revealed significant inhibition of CI (NADH dehydrogenase) and CIV (cytochrome c oxidase); this result was further supported by a decrease in the protein content of both complexes. Finally, we unveiled an impaired oxidation of glucose and larger reliance on long-chain fatty acids oxidation. Altogether, our findings clearly indicate a rewiring of the mitochondrial metabolic phenotype in the KMT2D-null or loss-of-function context that might contribute to the development of Kabuki disease, and represents metabolic reprogramming as a potential new therapeutic approach."xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.org/dc/terms/identifier | "doi:10.3390/cells9071685"xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/author | "Pucci P."xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/author | "Amoresano A."xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/author | "Lee J.E."xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/author | "Merla G."xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/author | "Piccoli C."xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/author | "Ge K."xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/author | "Capitanio N."xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/author | "Malerba N."xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/author | "Squeo G.M."xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/author | "Pinto G."xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/author | "Pacelli C."xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/author | "Adipietro I."xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/name | "Cells"xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/pages | "E1685"xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/title | "Loss of Function of the Gene Encoding the Histone Methyltransferase KMT2D Leads to Deregulation of Mitochondrial Respiration."xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://purl.uniprot.org/core/volume | "9"xsd:string |
| http://purl.uniprot.org/citations/32668765 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32668765 |
| http://purl.uniprot.org/citations/32668765 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/32668765 |
| http://purl.uniprot.org/uniprot/#_A0A0A0MQ73-mappedCitation-32668765 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32668765 |
| http://purl.uniprot.org/uniprot/#_A0A2S0X0M0-mappedCitation-32668765 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32668765 |
| http://purl.uniprot.org/uniprot/#_O14686-mappedCitation-32668765 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32668765 |