BH3-only protein Bim inhibits activity of antiapoptotic members of Bcl-2 family when expressed in yeast

• Published in: FEBS letters 2011-09, Vol.585 (17), p.2709-2713
• Main Authors: Juhásová, Barbora, Mentel, Marek, Bhatia-Kiššová, Ingrid, Zeman, Igor, Kolarov, Jordan, Forte, Michael, Polčic, Peter
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - genetics; Apoptosis - physiology; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Bax; bcl-2 Homologous Antagonist-Killer Protein - genetics; bcl-2 Homologous Antagonist-Killer Protein - metabolism; Bcl-2 homology domain; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Bcl-2-Like Protein 11; Bcl-X L; bcl-X Protein - genetics; bcl-X Protein - metabolism; Bcl-XL; BH domain; BH3-only proteins; Bim; Cell Fractionation; haemagglutinin; Immunoblotting; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mitochondrial Membranes - metabolism; Permeability; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; synthetic complete media; VDAC; voltage-dependent anion channel; Yeast
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2011.07.027

► BH3-only protein Bim was studied by coexpression with other Bcl-2 proteins in yeast. ► In this model, Bim activates Bax/Bak indirectly by inhibition of Bcl-X L/Bcl-2. ► Activity of Bim is not dependent on the presence of VDAC in the outer mitochondrial membrane. Proteins of the Bcl-2 family regulate programmed cell death in mammals by promoting the release of cytochrome c from mitochondria in response to various proapoptotic stimuli. The mechanism by which BH3-only members of the family activate multidomain proapoptotic proteins Bax and Bak to form a pore in mitochondrial membranes remains under dispute. We report that cell death promoting activity of BH3-only protein Bim can be reconstituted in yeast when both Bax and antiapoptotic protein Bcl-X L are present, suggesting that Bim likely activates Bax indirectly by inhibiting antiapoptotic proteins.