Mito-priming as a method to engineer Bcl-2 addiction

Abstract: Most apoptotic stimuli require mitochondrial outer membrane permeabilization (MOMP) in order to execute cell death. As such, MOMP is subject to tight control by Bcl-2 family proteins. We have developed a powerful new technique to investigate Bcl-2-mediated regulation of MOMP. This method, called mito-priming, uses co-expression of pro- and anti-apoptotic Bcl-2 proteins to engineer Bcl-2 addiction. On addition of Bcl-2 targeting BH3 mimetics, mito-primed cells undergo apoptosis in a rapid and synchronous manner. Using this method we have comprehensively surveyed the efficacy of BH3 mimetic compounds, identifying potent and specific MCL-1 inhibitors. Furthermore, by combining different pro- and anti-apoptotic Bcl-2 pairings together with CRISPR/Cas9-based genome editing, we find that tBID and PUMA can preferentially kill in a BAK-dependent manner. In summary, mito-priming represents a facile and robust means to trigger mitochondrial apoptosis

Objekt anzeigen

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Nature communications. - 7 (2016) , 10538, ISSN: 2041-1723

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2019
• Urheber: Lopez, Jonathan ; Bessou, Margaux ; Riley, Joel S. ; Giampazolias, Evangelos ; Fimm-Todt, Franziska ; Rochegüe, Tony ; Oberst, Andrew ; Green, Douglas R. ; Edlich, Frank ; Ichim, Gabriel ; Tait, Stephen W. G.
• Beteiligte Personen und Organisationen: Zentrum für Biochemie und Molekulare Zellforschung

Weitere Informationen

• DOI: 10.1038/ncomms10538
• URN: urn:nbn:de:bsz:25-freidok-1365023
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.