Hippe, Diana

[["dc.bibliographiccitation.firstpage","150"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Microbial Cell"],["dc.bibliographiccitation.lastpage","162"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Graumann, Kristin"],["dc.contributor.author","Schaumburg, Frieder"],["dc.contributor.author","Reubold, Thomas"],["dc.contributor.author","Hippe, Diana"],["dc.contributor.author","Eschenburg, Susanne"],["dc.contributor.author","Lüder, Carsten G. K."],["dc.date.accessioned","2019-07-09T11:42:42Z"],["dc.date.available","2019-07-09T11:42:42Z"],["dc.date.issued","2015"],["dc.description.abstract","Inhibition of programmed cell death pathways of mammalian cells often facilitates the sustained survival of intracellular microorganisms. The apicomplexan parasite Toxoplasma gondii is a master regulator of host cell apoptotic pathways. Here, we have characterized a novel anti-apoptotic activity of T. gondii. Using a cell-free cytosolic extract model, we show that T. gondii interferes with the activities of caspase 9 and caspase 3/7 which have been induced by exogenous cytochrome c and dATP. Proteolytic cleavage of caspases 9 and 3 is also diminished suggesting inhibition of holo-apoptosome function. Parasite infection of Jurkat T cells and subsequent triggering of apoptosome formation by exogenous cytochrome c in vitro and in vivo indicated that T. gondii also interferes with caspase activation in infected cells. Importantly, parasite inhibition of cytochrome c-induced caspase activation considerably contributes to the overall anti-apoptotic activity of T. gondii as observed in staurosporine-treated cells. Co-immunoprecipitation showed that T. gondii abolishes binding of caspase 9 to Apaf-1 whereas the interaction of cytochrome c with Apaf-1 remains unchanged. Finally, T. gondii lysate mimics the effect of viable parasites and prevents holo-apoptosome functionality in a reconstituted in vitro system comprising recombinant Apaf-1 and caspase 9. Beside inhibition of cytochrome c release from host cell mitochondria, T. gondii thus also targets the holo-apoptosome assembly as a second mean to efficiently inhibit the caspase-dependent intrinsic cell death pathway."],["dc.identifier.doi","10.15698/mic2015.05.201"],["dc.identifier.fs","618353"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13656"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58731"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.issn","2311-2638"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Toxoplasma gondii inhibits cytochrome c-induced caspase activation in its host cell by interference with holo-apoptosome assembly"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]