| http://purl.uniprot.org/citations/32385113 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32385113 | http://www.w3.org/2000/01/rdf-schema#comment | "Mitochondrial dysfunction has long been implicated in the neurodegenerative disorder Parkinson's disease (PD); however, it is unclear how mitochondrial impairment and α-synuclein pathology are coupled. Using specific mitochondrial inhibitors, EM analysis, and biochemical assays, we report here that intramitochondrial protein homeostasis plays a major role in α-synuclein aggregation. We found that interference with intramitochondrial proteases, such as HtrA2 and Lon protease, and mitochondrial protein import significantly aggravates α-synuclein seeding. In contrast, direct inhibition of mitochondrial complex I, an increase in intracellular calcium concentration, or formation of reactive oxygen species, all of which have been associated with mitochondrial stress, did not affect α-synuclein pathology. We further demonstrate that similar mechanisms are involved in amyloid-β 1-42 (Aβ42) aggregation. Our results suggest that, in addition to other protein quality control pathways, such as the ubiquitin-proteasome system, mitochondria per se can influence protein homeostasis of cytosolic aggregation-prone proteins. We propose that approaches that seek to maintain mitochondrial fitness, rather than target downstream mitochondrial dysfunction, may aid in the search for therapeutic strategies to manage PD and related neuropathologies."xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.ra119.011650"xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/author | "Lu M."xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/author | "Mishra A."xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/author | "Kaminski C.F."xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/author | "Stephens A.D."xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/author | "Kaminski Schierle G.S."xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/author | "Hockings C."xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/author | "Lautenschlager J."xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/author | "Rees E.J."xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/author | "Fantham M.J."xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/author | "Fernandez-Villegas A."xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/author | "Manton J.D."xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/author | "Wagner-Valladolid S."xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/pages | "10138-10152"xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/title | "Intramitochondrial proteostasis is directly coupled to alpha-synuclein and amyloid beta1-42 pathologies."xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://purl.uniprot.org/core/volume | "295"xsd:string |
| http://purl.uniprot.org/citations/32385113 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32385113 |
| http://purl.uniprot.org/citations/32385113 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/32385113 |
| http://purl.uniprot.org/uniprot/#_A0A0A0MRG2-mappedCitation-32385113 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32385113 |
| http://purl.uniprot.org/uniprot/#_A0A8F9R5D5-mappedCitation-32385113 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32385113 |
| http://purl.uniprot.org/uniprot/#_A0A140VJC8-mappedCitation-32385113 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32385113 |