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dc.contributor.authorByun, J.-
dc.contributor.authorSon, Sm-
dc.contributor.authorCha, M-Y-
dc.contributor.authorShong, M.-
dc.contributor.authorHwang, Y. J.-
dc.contributor.authorKim, Y.-
dc.contributor.authorRyu, H.-
dc.contributor.authorMoon, M.-
dc.contributor.authorKim, K-S-
dc.contributor.authorMook-Jung, I.-
dc.date.accessioned2024-01-20T07:01:47Z-
dc.date.available2024-01-20T07:01:47Z-
dc.date.created2021-09-05-
dc.date.issued2015-06-
dc.identifier.issn1350-9047-
dc.identifier.urihttps://pubs.kist.re.kr/handle/201004/125392-
dc.description.abstractMitochondrial dysfunction, often characterized by massive fission and other morphological abnormalities, is a well-known risk factor for Alzheimer's disease (AD). One causative mechanism underlying AD-associated mitochondrial dysfunction is thought to be amyloid-beta (A beta), yet the pathways between A beta and mitochondrial dysfunction remain elusive. In this study, we report that CR6-interacting factor 1 (Crif1), a mitochondrial inner membrane protein, is a key player in A beta-induced mitochondrial dysfunction. Specifically, we found that Crif1 levels were downregulated in the pathological regions of Tg6799 mice brains, wherein overexpressed A beta undergoes self-aggregation. Downregulation of Crif1 was similarly observed in human AD brains as well as in SH-SY5Y cells treated with A beta. In addition, knockdown of Crif1, using RNA interference, induced mitochondrial dysfunction with phenotypes similar to those observed in A beta-treated cells. Conversely, Crif1 overexpression prevented A beta-induced mitochondrial dysfunction and cell death. Finally, we show that A beta-induced downregulation of Crif1 is mediated by enhanced reactive oxygen species (ROS) and ROS-dependent sumoylation of the transcription factor specificity protein 1 (Sp1). These results identify the ROS-Sp1-Crif1 pathway to be a new mechanism underlying A beta-induced mitochondrial dysfunction and suggest that ROS-mediated downregulation of Crif1 is a crucial event in AD pathology. We propose that Crif1 may serve as a novel therapeutic target in the treatment of AD.-
dc.languageEnglish-
dc.publisherNATURE PUBLISHING GROUP-
dc.subjectOXIDATIVE STRESS-
dc.subjectATP SYNTHASE-
dc.subjectNEURODEGENERATIVE DISEASES-
dc.subjectCELL-PROLIFERATION-
dc.subjectCRISTAE MORPHOLOGY-
dc.subjectCORTICAL-NEURONS-
dc.subjectPLAQUE-FORMATION-
dc.subjectTRANSGENIC MICE-
dc.subjectANIMAL-MODEL-
dc.subjectIN-VIVO-
dc.titleCR6-interacting factor 1 is a key regulator in A beta-induced mitochondrial disruption and pathogenesis of Alzheimer's disease-
dc.typeArticle-
dc.identifier.doi10.1038/cdd.2014.184-
dc.description.journalClass1-
dc.identifier.bibliographicCitationCELL DEATH AND DIFFERENTIATION, v.22, no.6, pp.959 - 973-
dc.citation.titleCELL DEATH AND DIFFERENTIATION-
dc.citation.volume22-
dc.citation.number6-
dc.citation.startPage959-
dc.citation.endPage973-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.identifier.wosid000353916700009-
dc.identifier.scopusid2-s2.0-84939985504-
dc.relation.journalWebOfScienceCategoryBiochemistry & Molecular Biology-
dc.relation.journalWebOfScienceCategoryCell Biology-
dc.relation.journalResearchAreaBiochemistry & Molecular Biology-
dc.relation.journalResearchAreaCell Biology-
dc.type.docTypeArticle-
dc.subject.keywordPlusOXIDATIVE STRESS-
dc.subject.keywordPlusATP SYNTHASE-
dc.subject.keywordPlusNEURODEGENERATIVE DISEASES-
dc.subject.keywordPlusCELL-PROLIFERATION-
dc.subject.keywordPlusCRISTAE MORPHOLOGY-
dc.subject.keywordPlusCORTICAL-NEURONS-
dc.subject.keywordPlusPLAQUE-FORMATION-
dc.subject.keywordPlusTRANSGENIC MICE-
dc.subject.keywordPlusANIMAL-MODEL-
dc.subject.keywordPlusIN-VIVO-
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