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dc.contributor.authorMasaldan, S
dc.contributor.authorClatworthy, SAS
dc.contributor.authorGamell, C
dc.contributor.authorSmith, ZM
dc.contributor.authorFrancis, PS
dc.contributor.authorDenoyer, D
dc.contributor.authorMeggyesy, PM
dc.contributor.authorLa Fontaine, S
dc.contributor.authorCater, MA
dc.date.accessioned2020-12-10T00:28:15Z
dc.date.available2020-12-10T00:28:15Z
dc.date.issued2018-06-01
dc.identifierpii: S2213-2317(18)30081-8
dc.identifier.citationMasaldan, S., Clatworthy, S. A. S., Gamell, C., Smith, Z. M., Francis, P. S., Denoyer, D., Meggyesy, P. M., La Fontaine, S. & Cater, M. A. (2018). Copper accumulation in senescent cells: Interplay between copper transporters and impaired autophagy. REDOX BIOLOGY, 16, pp.322-331. https://doi.org/10.1016/j.redox.2018.03.007.
dc.identifier.issn2213-2317
dc.identifier.urihttp://hdl.handle.net/11343/253499
dc.description.abstractCellular senescence is characterized by irreversible growth arrest incurred through either replicative exhaustion or by pro-oncogenic cellular stressors (radioactivity, oxidative stress, oncogenic activation). The enrichment of senescent cells in tissues with age has been associated with tissue dyshomeostasis and age-related pathologies including cancers, neurodegenerative disorders (e.g. Alzheimer's, Parkinson's, etc.) and metabolic disorders (e.g. diabetes). We identified copper accumulation as being a universal feature of senescent cells [mouse embryonic fibroblasts (MEF), human prostate epithelial cells and human diploid fibroblasts] in vitro. Elevated copper in senescent MEFs was accompanied by elevated levels of high-affinity copper uptake protein 1 (Ctr1), diminished levels of copper-transporting ATPase 1 (Atp7a) (copper export) and enhanced antioxidant defence reflected by elevated levels of glutathione (GSH), superoxide dismutase 1 (SOD1) and glutaredoxin 1 (Grx1). The levels of intracellular copper were further increased in senescent MEFs cultured in copper supplemented medium and in senescent Mottled Brindled (Mobr) MEFs lacking functional Atp7a. Finally, we demonstrated that the restoration/preservation of autophagic-lysosomal degradation in senescent MEFs following rapamycin treatment correlated with attenuation of copper accumulation in these cells despite a further decrease in Atp7a levels. This study for the first time establishes a link between Atp7a and the autophagic-lysosomal pathway, and a requirement for both to effect efficient copper export. Such a connection between cellular autophagy and copper homeostasis is significant, as both have emerged as important facets of age-associated degenerative disease.
dc.languageEnglish
dc.publisherELSEVIER SCIENCE BV
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.titleCopper accumulation in senescent cells: Interplay between copper transporters and impaired autophagy
dc.typeJournal Article
dc.identifier.doi10.1016/j.redox.2018.03.007
melbourne.affiliation.departmentClinical Pathology
melbourne.affiliation.departmentBio21
melbourne.affiliation.departmentFlorey Department of Neuroscience and Mental Health
melbourne.source.titleRedox Biology
melbourne.source.volume16
melbourne.source.pages322-331
melbourne.identifier.nhmrc1027125
dc.rights.licenseCC BY-NC-ND
melbourne.elementsid1320081
melbourne.contributor.authorGamell-Fulla, Cristina
melbourne.contributor.authorCater, Michael
melbourne.contributor.authorMasaldan, Shashank
dc.identifier.eissn2213-2317
melbourne.identifier.fundernameidNHMRC, 1027125
melbourne.accessrightsOpen Access


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