| http://purl.uniprot.org/citations/29576218 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29576218 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29576218 | http://www.w3.org/2000/01/rdf-schema#comment | "Mitochondrial disorders causing neurodegeneration in childhood are genetically heterogeneous, and the underlying genetic etiology remains unknown in many affected individuals. We identified biallelic variants in PMPCB in individuals of four families including one family with two affected siblings with neurodegeneration and cerebellar atrophy. PMPCB encodes the catalytic subunit of the essential mitochondrial processing protease (MPP), which is required for maturation of the majority of mitochondrial precursor proteins. Mitochondria isolated from two fibroblast cell lines and induced pluripotent stem cells derived from one affected individual and differentiated neuroepithelial stem cells showed reduced PMPCB levels and accumulation of the processing intermediate of frataxin, a sensitive substrate for MPP dysfunction. Introduction of the identified PMPCB variants into the homologous S. cerevisiae Mas1 protein resulted in a severe growth and MPP processing defect leading to the accumulation of mitochondrial precursor proteins and early impairment of the biogenesis of iron-sulfur clusters, which are indispensable for a broad range of crucial cellular functions. Analysis of biopsy materials of an affected individual revealed changes and decreased activity in iron-sulfur cluster-containing respiratory chain complexes and dysfunction of mitochondrial and cytosolic Fe-S cluster-dependent enzymes. We conclude that biallelic mutations in PMPCB cause defects in MPP proteolytic activity leading to dysregulation of iron-sulfur cluster biogenesis and triggering a complex neurological phenotype of neurodegeneration in early childhood."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajhg.2018.02.014"xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajhg.2018.02.014"xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Matsumoto N."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Matsumoto N."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Miyake N."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Miyake N."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Shinde D.N."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Shinde D.N."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Larson A."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Larson A."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Burnett A."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Burnett A."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Stephani U."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Stephani U."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Voegtle F.N."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Voegtle F.N."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Helbig I."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Helbig I."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Helbig K.L."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Helbig K.L."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Pendziwiat M."xsd:string |
| http://purl.uniprot.org/citations/29576218 | http://purl.uniprot.org/core/author | "Pendziwiat M."xsd:string |