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dc.contributor.authorGuida M
dc.contributor.authorZanon A
dc.contributor.authorMontibeller L
dc.contributor.authorLavdas AA
dc.contributor.authorLadurner J
dc.contributor.authorPischedda F
dc.contributor.authorRakovic A
dc.contributor.authorDomingues FS
dc.contributor.authorPiccoli G
dc.contributor.authorKlein C
dc.contributor.authorPramstaller PP
dc.contributor.authorHicks AA
dc.contributor.authorPichler I
dc.date.accessioned2019-02-25T09:30:42Z
dc.date.available2019-02-25T09:30:42Z
dc.date.issued2019
dc.identifier.issn1661-6596
dc.identifier.urihttp://dx.doi.org/10.3390/ijms20030748
dc.identifier.urihttp://hdl.handle.net/10863/8757
dc.description.abstractMutations in the PRKN gene (encoding parkin) have been linked to the most frequent known cause of recessive Parkinson's disease (PD), and parkin dysfunction represents a risk factor for sporadic PD. Parkin is widely neuroprotective through different cellular pathways, as it protects dopaminergic neurons from apoptosis in a series of cellular and animal models of PD. The mitochondrial protein apoptosis-inducing factor (AIF) is an important cell death effector, which, upon cellular stress in many paradigms, is redistributed from the mitochondria to the nucleus to function as a proapoptotic factor, mostly independent of caspase activity, while in normal mitochondria it functions as an antiapoptotic factor. AIF is known to participate in dopaminergic neuron loss in experimental PD models and in patients with PD. We, therefore, investigated possible crosstalk between parkin and AIF. By using immunoprecipitation and proximity ligation assays, we demonstrated a physical interaction between the two proteins. Nuclear AIF translocation was significantly reduced by parkin expression in neuroblastoma SH-SY5Y cells after exposure to an apoptogenic stimulus. These results were confirmed in primary murine cortical neurons, which showed a higher nuclear translocation of AIF in parkin-deficient neurons upon an excitotoxic stimulus. Our results indicate that the interaction of parkin with AIF interferes with the nuclear translocation of AIF, which might contribute to the neuroprotective activity of parkin.en_US
dc.languageEnglish
dc.language.isoenen_US
dc.relation
dc.rights
dc.titleParkin Interacts with Apoptosis-Inducing Factor and Interferes with Its Translocation to the Nucleus in Neuronal Cellsen_US
dc.typeArticleen_US
dc.date.updated2019-02-24T21:27:18Z
dc.language.isiEN-GB
dc.journal.titleInternational Journal of Molecular Sciences
dc.description.fulltextopenen_US


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