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Article: Nitration of Drp1 provokes mitophagy activation mediating neuronal injury in experimental autoimmune encephalomyelitis

TitleNitration of Drp1 provokes mitophagy activation mediating neuronal injury in experimental autoimmune encephalomyelitis
Authors
KeywordsDynamin-related protein 1
Nitration
Mitophagy
Neuronal damages
Multiple sclerosis
Issue Date2019
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/freeradbiomed
Citation
Free Radical Biology & Medicine, 2019, v. 143, p. 70-83 How to Cite?
AbstractActive autophagy/mitophagy could mediate neurodegeneration and motor disabilities in multiple sclerosis (MS). Mitochondrial recruitment of dynamin-related protein 1 (Drp1) is a crucial step to initiate mitophagy. Peroxynitrite (ONOO−) could be a player in MS pathology but the mechanisms remain unknown. We used animal model of experimental autoimmune encephalomyelitis (EAE) and tested whether ONOO− mediates Drp1 assembly in mitochondria for mitophagy and aggravates MS pathology. We found that autophagy/mitophagy activation was coincidently increased with axonal damage, apoptosis and disease progression in active EAE mice, which were remarkably attenuated by mitochondrial division/mitophagy inhibitor Mdivi-1. Importantly, increased ONOO− production was companied with Drp1 mitochondrial recruitment, PINK1/Parkin-mediated mitophagy, axonal degeneration and neuronal cell death, which were reversed by peroxynitrite decomposition catalyst (PDC). Furthermore, ONOO− production induced Drp1 nitration, promoted Drp1 assembly and mitochondrial recruitment for mitophagy activation, contributing to the EAE pathology. Together, we conclude that ONOO− serves as a key mediator in Drp1 nitration modification and assembly for facilitating mitophagy activation. Targeting ONOO−-mediated Drp1 assembly and mitochondrial recruitment could be an important therapeutic strategy for multiple sclerosis treatment.
Persistent Identifierhttp://hdl.handle.net/10722/273843
ISSN
2017 Impact Factor: 6.02
2015 SCImago Journal Rankings: 2.468

 

DC FieldValueLanguage
dc.contributor.authorLI, W-
dc.contributor.authorFENG, J-
dc.contributor.authorGao, C-
dc.contributor.authorWU, M-
dc.contributor.authorDU, Q-
dc.contributor.authorTsoi, B-
dc.contributor.authorWang, Q-
dc.contributor.authorYang, D-
dc.contributor.authorShen, J-
dc.date.accessioned2019-08-18T14:49:42Z-
dc.date.available2019-08-18T14:49:42Z-
dc.date.issued2019-
dc.identifier.citationFree Radical Biology & Medicine, 2019, v. 143, p. 70-83-
dc.identifier.issn0891-5849-
dc.identifier.urihttp://hdl.handle.net/10722/273843-
dc.description.abstractActive autophagy/mitophagy could mediate neurodegeneration and motor disabilities in multiple sclerosis (MS). Mitochondrial recruitment of dynamin-related protein 1 (Drp1) is a crucial step to initiate mitophagy. Peroxynitrite (ONOO−) could be a player in MS pathology but the mechanisms remain unknown. We used animal model of experimental autoimmune encephalomyelitis (EAE) and tested whether ONOO− mediates Drp1 assembly in mitochondria for mitophagy and aggravates MS pathology. We found that autophagy/mitophagy activation was coincidently increased with axonal damage, apoptosis and disease progression in active EAE mice, which were remarkably attenuated by mitochondrial division/mitophagy inhibitor Mdivi-1. Importantly, increased ONOO− production was companied with Drp1 mitochondrial recruitment, PINK1/Parkin-mediated mitophagy, axonal degeneration and neuronal cell death, which were reversed by peroxynitrite decomposition catalyst (PDC). Furthermore, ONOO− production induced Drp1 nitration, promoted Drp1 assembly and mitochondrial recruitment for mitophagy activation, contributing to the EAE pathology. Together, we conclude that ONOO− serves as a key mediator in Drp1 nitration modification and assembly for facilitating mitophagy activation. Targeting ONOO−-mediated Drp1 assembly and mitochondrial recruitment could be an important therapeutic strategy for multiple sclerosis treatment.-
dc.languageeng-
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/freeradbiomed-
dc.relation.ispartofFree Radical Biology & Medicine-
dc.subjectDynamin-related protein 1-
dc.subjectNitration-
dc.subjectMitophagy-
dc.subjectNeuronal damages-
dc.subjectMultiple sclerosis-
dc.titleNitration of Drp1 provokes mitophagy activation mediating neuronal injury in experimental autoimmune encephalomyelitis-
dc.typeArticle-
dc.identifier.emailGao, C: colingao@hku.hk-
dc.identifier.emailTsoi, B: amytsoi@hku.hk-
dc.identifier.emailYang, D: yangdan@hku.hk-
dc.identifier.emailShen, J: shenjg@hku.hk-
dc.identifier.authorityYang, D=rp00825-
dc.identifier.authorityShen, J=rp00487-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.freeradbiomed.2019.07.037-
dc.identifier.pmid31377418-
dc.identifier.scopuseid_2-s2.0-85070228669-
dc.identifier.hkuros301764-
dc.identifier.volume143-
dc.identifier.spage70-
dc.identifier.epage83-
dc.publisher.placeUnited States-

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