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Authordc.contributor.authorUrrutia, Pamela J. 
Authordc.contributor.authorAguirre, Pabla 
Authordc.contributor.authorTapia, Victoria 
Authordc.contributor.authorCarrasco, Carlos M. 
Authordc.contributor.authorMena, Natalia P. 
Authordc.contributor.authorNúñez González, Marco 
Cita de ítemdc.identifier.citationBBA - Molecular Basis of Disease 1863 (2017) 2202–2209es_ES
Abstractdc.description.abstractMitochondrial dysfunction and oxidative damage, often accompanied by elevated intracellular iron levels, are pathophysiological features in a number of neurodegenerative processes. The question arises as to whether iron dyshomeostasis is a consequence of mitochondrial dysfunction. Here we have evaluated the role of Iron Regulatory Protein 1 (IRP1) in the death of SH-SY5Y dopaminergic neuroblastoma cells subjected to mitochondria complex I inhibition. We found that complex I inhibition was associated with increased levels of transferrin receptor 1 (TfR1) and iron uptake transporter divalent metal transporter 1 (DMT1), and decreased levels of iron efflux transporter Ferroportin 1 (FPN1), together with increased 55Fe uptake activity and an increased cytoplasmic labile iron pool. Complex I inhibition also resulted in increased oxidative modifications and increased cysteine oxidation that were inhibited by the iron chelators desferoxamine, M30 and Q1. Silencing of IRP1 abolished the rotenone-induced increase in 55Fe uptake activity and it protected cells from death induced by complex I inhibition. IRP1 knockdown cells presented higher ferritin levels, a lower iron labile pool, increased resistance to cysteine oxidation and decreased oxidative modifications. These results support the concept that IRP1 is an oxidative stress biosensor that mediates iron accumulation and cell death when deregulated by mitochondrial dysfunction. IRP1 activation, secondary to mitochondrial dysfunction, may underlie the events leading to iron dyshomeostasis and neuronal death observed in neurodegenerative disorders with an iron accumulation component.es_ES
Patrocinadordc.description.sponsorshipFondo Nacional de Ciencia y Tecnología (FONDECYT) number 1130068es_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile*
Link to Licensedc.rights.uri*
Sourcedc.sourceBBA - Molecular Basis of Diseasees_ES
Keywordsdc.subjectMitochondrial dysfunctiones_ES
Keywordsdc.subjectIron accumulationes_ES
Keywordsdc.subjectOxidative damagees_ES
Títulodc.titleCell death induced by mitochondrial complex I inhibition is mediated by Iron Regulatory Proteines_ES
Document typedc.typeArtículo de revistaes_ES
Indexationuchile.indexArtículo de publicación ISIes_ES

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Attribution-NonCommercial-NoDerivs 3.0 Chile
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile