title: Bak and Bax are non-redundant during infection- and DNA damage-induced apoptosis.
abstract: Mitochondrial outer membrane permeabilization (MOMP) and release of mitochondrial intermembrane proteins like cytochrome c are critical steps in the control of apoptosis. Previous work has shown that MOMP depends on the functionally redundant multidomain proapoptotic proteins, Bak and Bax. Here we demonstrate that Bak and Bax are functionally non-redundant during Neisseria gonorrhoeae (Ngo)- and cisplatin-induced apoptosis. While the activation of Bak is caspase independent Bax activation needs Bak and active caspases. Silencing of either Bak or Bax resists both Ngo- and cisplatin- but not TNFalpha-induced apoptosis. Activation of Bak is required to release cytochrome c from the mitochondria; however, Bax is still required to activate effector caspases. Thus, both Bak and Bax are necessary to accomplish DNA damage and Ngo-induced apoptosis.
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Research Group for Molecular Infection and Tumor Biology, Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kepp
authors.forename: Krishnaraj
authors.initials: K
authors.lastname: Rajalingam
authors.forename: Sonja
authors.initials: S
authors.lastname: Kimmig
authors.forename: Thomas
authors.initials: T
authors.lastname: Rudel
mesh_terms: D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002458:Cell Fractionation; D004249:DNA Damage; D017931:DNA Primers; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D007425:Intracellular Membranes / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D009344:Neisseria gonorrhoeae; D010539:Permeability; D034622:RNA Interference; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C494772:BAK1 protein, human; C494826:BAX protein, human; D017931:DNA Primers; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D020169:Caspases