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dc.contributor.authorZhou, Heng
dc.contributor.authorForveille, Sabrina
dc.contributor.authorSauvat, Allan
dc.contributor.authorSica, Valentina
dc.contributor.authorIzzo, Valentina
dc.contributor.authorDurand, Sylvère
dc.contributor.authorMüller, Kevin
dc.contributor.authorLiu, Peng
dc.contributor.authorZitvogel, Laurence
dc.contributor.authorRekdal, Øystein
dc.contributor.authorKepp, Oliver
dc.contributor.authorKroemer, Guido
dc.date.accessioned2022-04-19T08:43:00Z
dc.date.available2022-04-19T08:43:00Z
dc.date.issued2015-09-10
dc.description.abstractLTX-315 has been developed as an amphipathic cationic peptide that kills cancer cells. Here, we investigated the putative involvement of mitochondria in the cytotoxic action of LTX-315. Subcellular fractionation of LTX-315-treated cells, followed by mass spectrometric quantification, revealed that the agent was enriched in mitochondria. LTX-315 caused an immediate arrest of mitochondrial respiration without any major uncoupling effect. Accordingly, LTX-315 disrupted the mitochondrial network, dissipated the mitochondrial inner transmembrane potential, and caused the release of mitochondrial intermembrane proteins into the cytosol. LTX-315 was relatively inefficient in stimulating mitophagy. Cells lacking the two pro-apoptotic multidomain proteins from the BCL-2 family, BAX and BAK, were less susceptible to LTX-315-mediated killing. Moreover, cells engineered to lose their mitochondria (by transfection with Parkin combined with treatment with a protonophore causing mitophagy) were relatively resistant against LTX-315, underscoring the importance of this organelle for LTX-315-mediated cytotoxicity. Altogether, these results support the notion that LTX-315 kills cancer cells by virtue of its capacity to permeabilize mitochondrial membranes.en_US
dc.identifier.citationZhou, Forveille, Sauvat, Sica, Izzo, Durand, Müller, Liu P, Zitvogel L, Rekdal Ø, Kepp O, Kroemer G. The oncolytic peptide LTX-315 kills cancer cells through Bax/Bak-regulated mitochondrial membrane permeabilization. OncoTarget. 2015;6(29):26599-26614en_US
dc.identifier.cristinIDFRIDAID 1332090
dc.identifier.doi10.18632/oncotarget.5613
dc.identifier.issn1949-2553
dc.identifier.urihttps://hdl.handle.net/10037/24799
dc.language.isoengen_US
dc.publisherImpact Journalsen_US
dc.relation.journalOncoTarget
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2015 The Author(s)en_US
dc.titleThe oncolytic peptide LTX-315 kills cancer cells through Bax/Bak-regulated mitochondrial membrane permeabilizationen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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