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http://purl.uniprot.org/citations/31361992http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/31361992http://www.w3.org/2000/01/rdf-schema#comment"Corneal endothelium (CE) is a monolayer of mitochondria-rich cells, critical for maintaining corneal transparency compatible with clear vision. Fuchs endothelial corneal dystrophy (FECD) is a heterogeneous, genetically complex disorder, where oxidative stress plays a key role in the rosette formation during the degenerative loss of CE. Increased mitochondrial fragmentation along with excessive mitophagy activation has been detected in FECD; however, the mechanism of aberrant mitochondrial dynamics in CE cell loss is poorly understood. Here, the role of oxidative stress in mitophagy activation in FECD is investigated. Immunoblotting of FECD ex vivo specimens revealed an accumulation of PINK1 and phospho-Parkin (Ser65) along with loss of total Parkin and total Drp1. Similarly, modeling of rosette formation with menadione (MN), led to phospho-Parkin accumulation in fragmented mitochondria resulting in mitophagy-induced mitochondrial clearance, albeit possibly in a PINK1-independent manner. Loss of PINK1, phospho-Drp1, and total Drp1 was prominent after MN-induced oxidative stress, but not after mitochondrial depolarization by carbonyl cyanide m-chlorophenyl hydrazone. Moreover, MN-induced mitophagy led to degradation of Parkin along with sequestration of Drp1 and PINK1 that was rescued by mitophagy inhibition. This study shows that in FECD, intracellular oxidative stress induces Parkin-mediated mitochondrial fragmentation where endogenous Drp1 and PINK1 are sequestered and degraded by mitophagy during degenerative loss of post-mitotic cells of ocular tissue."xsd:string
http://purl.uniprot.org/citations/31361992http://purl.org/dc/terms/identifier"doi:10.1016/j.ajpath.2019.06.012"xsd:string
http://purl.uniprot.org/citations/31361992http://purl.uniprot.org/core/author"Chen Y."xsd:string
http://purl.uniprot.org/citations/31361992http://purl.uniprot.org/core/author"Kumar V."xsd:string
http://purl.uniprot.org/citations/31361992http://purl.uniprot.org/core/author"Deshpande N."xsd:string
http://purl.uniprot.org/citations/31361992http://purl.uniprot.org/core/author"Benischke A.S."xsd:string
http://purl.uniprot.org/citations/31361992http://purl.uniprot.org/core/author"Vasanth S."xsd:string
http://purl.uniprot.org/citations/31361992http://purl.uniprot.org/core/author"Jurkunas U.V."xsd:string
http://purl.uniprot.org/citations/31361992http://purl.uniprot.org/core/author"Miyai T."xsd:string
http://purl.uniprot.org/citations/31361992http://purl.uniprot.org/core/author"Price M.O."xsd:string
http://purl.uniprot.org/citations/31361992http://purl.uniprot.org/core/author"Melangath G."xsd:string
http://purl.uniprot.org/citations/31361992http://purl.uniprot.org/core/author"Price F.W. Jr."xsd:string
http://purl.uniprot.org/citations/31361992http://purl.uniprot.org/core/date"2019"xsd:gYear
http://purl.uniprot.org/citations/31361992http://purl.uniprot.org/core/name"Am J Pathol"xsd:string
http://purl.uniprot.org/citations/31361992http://purl.uniprot.org/core/pages"2061-2076"xsd:string
http://purl.uniprot.org/citations/31361992http://purl.uniprot.org/core/title"Activation of PINK1-Parkin-Mediated Mitophagy Degrades Mitochondrial Quality Control Proteins in Fuchs Endothelial Corneal Dystrophy."xsd:string
http://purl.uniprot.org/citations/31361992http://purl.uniprot.org/core/volume"189"xsd:string
http://purl.uniprot.org/citations/31361992http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/31361992
http://purl.uniprot.org/citations/31361992http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/31361992
http://purl.uniprot.org/uniprot/#_D3JZW5-mappedCitation-31361992http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31361992
http://purl.uniprot.org/uniprot/#_D3K2X1-mappedCitation-31361992http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31361992
http://purl.uniprot.org/uniprot/#_D3K2X2-mappedCitation-31361992http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31361992
http://purl.uniprot.org/uniprot/#_A0A0S2Z446-mappedCitation-31361992http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31361992
http://purl.uniprot.org/uniprot/#_A0A0S2Z447-mappedCitation-31361992http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31361992