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Article: ROS-dependent regulation of parkin and DJ-1 localization during oxidative stress in neurons

TitleROS-dependent regulation of parkin and DJ-1 localization during oxidative stress in neurons
Authors
Issue Date2012
Citation
Human Molecular Genetics, 2012, v. 21, n. 22, p. 4888-4903 How to Cite?
AbstractMutations in several genes, including Parkin, PTEN-induced kinase 1 (Pink1) and DJ-1, are associated with rare inherited forms of Parkinson's disease (PD). Despite recent attention on the function of these genes, the interplay between DJ-1, Pink1 and Parkin in PD pathogenesis remains unclear. In particular, whether these genes regulate mitochondrial control pathways in neurons is highly controversial. Here we report that Pink1-dependent Parkin translocation does occur in mouse cortical neurons in response to a variety of mitochondrial damaging agents. This translocation only occurs in the absence of antioxidants in the neuronal culturing medium, implicating a key role of reactive oxygen species (ROS) in this response. Consistent with these observations, ROS blockers also prevent Parkin recruitment in mouse embryonic fibroblasts. Loss of DJ-1, a gene linked to ROS management, results in increased stress-induced Parkin recruitment and increased mitophagy. Expression of wild-type DJ-1, but not a cysteine-106 mutant associated with defective ROS response, rescues this accelerated Parkin recruitment. Interestingly, DJ-1 levels increase at mitochondria following oxidative damage in both fibroblasts and neurons, and this process also depends on Parkin and possibly Pink1. These results not only highlight the presence of a Parkin/Pink1-mediated pathway of mitochondrial quality control (MQC) in neurons, they also delineate a complex reciprocal relationship between DJ-1 and the Pink1/Parkin pathway of MQC. © The Author 2012. Published by Oxford University Press. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/292230
ISSN
2023 Impact Factor: 3.1
2023 SCImago Journal Rankings: 1.602
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorJoselin, Alvin P.-
dc.contributor.authorHewitt, Sarah J.-
dc.contributor.authorCallaghan, Steve M.-
dc.contributor.authorKim, Raymond H.-
dc.contributor.authorChung, Young Hwa-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorShen, Jie-
dc.contributor.authorSlack, Ruth S.-
dc.contributor.authorPark, David S.-
dc.date.accessioned2020-11-17T14:56:02Z-
dc.date.available2020-11-17T14:56:02Z-
dc.date.issued2012-
dc.identifier.citationHuman Molecular Genetics, 2012, v. 21, n. 22, p. 4888-4903-
dc.identifier.issn0964-6906-
dc.identifier.urihttp://hdl.handle.net/10722/292230-
dc.description.abstractMutations in several genes, including Parkin, PTEN-induced kinase 1 (Pink1) and DJ-1, are associated with rare inherited forms of Parkinson's disease (PD). Despite recent attention on the function of these genes, the interplay between DJ-1, Pink1 and Parkin in PD pathogenesis remains unclear. In particular, whether these genes regulate mitochondrial control pathways in neurons is highly controversial. Here we report that Pink1-dependent Parkin translocation does occur in mouse cortical neurons in response to a variety of mitochondrial damaging agents. This translocation only occurs in the absence of antioxidants in the neuronal culturing medium, implicating a key role of reactive oxygen species (ROS) in this response. Consistent with these observations, ROS blockers also prevent Parkin recruitment in mouse embryonic fibroblasts. Loss of DJ-1, a gene linked to ROS management, results in increased stress-induced Parkin recruitment and increased mitophagy. Expression of wild-type DJ-1, but not a cysteine-106 mutant associated with defective ROS response, rescues this accelerated Parkin recruitment. Interestingly, DJ-1 levels increase at mitochondria following oxidative damage in both fibroblasts and neurons, and this process also depends on Parkin and possibly Pink1. These results not only highlight the presence of a Parkin/Pink1-mediated pathway of mitochondrial quality control (MQC) in neurons, they also delineate a complex reciprocal relationship between DJ-1 and the Pink1/Parkin pathway of MQC. © The Author 2012. Published by Oxford University Press. All rights reserved.-
dc.languageeng-
dc.relation.ispartofHuman Molecular Genetics-
dc.titleROS-dependent regulation of parkin and DJ-1 localization during oxidative stress in neurons-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/hmg/dds325-
dc.identifier.pmid22872702-
dc.identifier.scopuseid_2-s2.0-84868087279-
dc.identifier.volume21-
dc.identifier.issue22-
dc.identifier.spage4888-
dc.identifier.epage4903-
dc.identifier.eissn1460-2083-
dc.identifier.isiWOS:000310369000007-
dc.identifier.issnl0964-6906-

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