Auto-activation of the Apoptosis Protein Bax Increases Mitochondrial Membrane Permeability and Is Inhibited

homology (BH) regions transform apoptosis signals into actions. The interactions between BH3 region-only proteins and multi-BH region proteins such as Bax and Bcl-2 have been proposed to be the dominant interactions required for initiating apoptosis. Experi-mental evidence also suggests that both homo- and hetero-interac-tions are mediated primarily by the BH3 regions in all Bcl-2 family proteins and contribute to commitment to or inhibition of apopto-sis.We found that a peptide containing theBH3helix of Baxwas not sufficient to activate recombinant Bax to permeabilize mitochon-dria. However, an extended peptide containing the BH3 helix and additional downstream sequences activated Bax to permeabilize mitochondria and liposomes. Bcl-2 inhibited the membrane-per-meabilizing activity of peptide-activated Bax. This activity of Bcl-2 was inhibited by the extended but not the BH3-only peptide despite both peptides binding to Bcl-2 with similar affinity. Further, mem