| http://purl.uniprot.org/citations/37399212 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/37399212 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutations in subunits of the mitochondrial NADH dehydrogenase cause mitochondrial complex I deficiency, a group of severe neurological diseases that can result in death in infancy. The pathogenesis of complex I deficiency remain poorly understood, and as a result there are currently no available treatments. To better understand the underlying mechanisms, we modelled complex I deficiency in Drosophila using knockdown of the mitochondrial complex I subunit ND-75 (NDUFS1) specifically in neurons. Neuronal complex I deficiency causes locomotor defects, seizures and reduced lifespan. At the cellular level, complex I deficiency does not affect ATP levels but leads to mitochondrial morphology defects, reduced endoplasmic reticulum-mitochondria contacts and activation of the endoplasmic reticulum unfolded protein response (UPR) in neurons. Multi-omic analysis shows that complex I deficiency dramatically perturbs mitochondrial metabolism in the brain. We find that expression of the yeast non-proton translocating NADH dehydrogenase NDI1, which reinstates mitochondrial NADH oxidation but not ATP production, restores levels of several key metabolites in the brain in complex I deficiency. Remarkably, NDI1 expression also reinstates endoplasmic reticulum-mitochondria contacts, prevents UPR activation and rescues the behavioural and lifespan phenotypes caused by complex I deficiency. Together, these data show that metabolic disruption due to loss of neuronal NADH dehydrogenase activity cause UPR activation and drive pathogenesis in complex I deficiency."xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pgen.1010793"xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/author | "Sweeney S.T."xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/author | "Vagnoni A."xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/author | "Chandel N.S."xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/author | "Chakrabarty R.P."xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/author | "Bateman J.M."xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/author | "Hirth F."xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/author | "Mattedi F."xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/author | "Granat L."xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/author | "Ranson D.C."xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/author | "Fort-Aznar L."xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/author | "Hamer E.L."xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/author | "Knorr D.Y."xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/name | "PLoS Genet"xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/pages | "e1010793"xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/title | "Yeast NDI1 reconfigures neuronal metabolism and prevents the unfolded protein response in mitochondrial complex I deficiency."xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://purl.uniprot.org/core/volume | "19"xsd:string |
| http://purl.uniprot.org/citations/37399212 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/37399212 |
| http://purl.uniprot.org/citations/37399212 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/37399212 |
| http://purl.uniprot.org/uniprot/#_P61851-mappedCitation-37399212 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37399212 |
| http://purl.uniprot.org/uniprot/#_A0A0B4KG56-mappedCitation-37399212 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37399212 |
| http://purl.uniprot.org/uniprot/#_A0A0B4KGJ5-mappedCitation-37399212 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37399212 |