A. Schematics illustrate the soluble Bax monomer and the MOM-bound Bax monomers, dimers and tetramers. The helices α2-α9 are depicted as cylinders with the indicated colors, and the helix α1 is omitted for simplicity. The MOM-bound tBid, depicted as a star, enhances cytosolic Bax interaction with the membrane (step I) and binds to the groove of Bax, thereby releasing α9 from the groove to the membrane (step II). The tBid binding also unfolds the Bax separating the latch (α6-α8) from the core (α2-α5) (step III). After tBid dissociates, the activated Bax monomer either embeds more hydrophobic regions such as α5 and α6 into the membrane (step IV) or binds other activated Bax monomer forming a BH3-in-groove dimer on the membrane surface (step V). After α5 is released into the membrane, the remnant BH3-in-groove dimer is rearranged to a α2-α3-α4 dimer (step VI). A Bax tetramer is then formed by two BH3-in-groove dimers via an additional dimer interface formed by two membrane-embedded α9 helices either intersected (step VII) or in parallel (step VIII). These Bax complexes may be in equilibrium with one another, but the BH3-in-groove dimerization is a prerequisite for the other dimerizations. In principle, combinations of these dimer interfaces would be sufficient to generate higher order oligomers, although other dimer interfaces have been discovered.B. A lipidic pore in the MOM is illustrated with BH3-in-groove dimers located on the cytosolic surface of the membrane and α9 monomer and dimer at the rim. Note that the BH3-in-groove dimers are partially embedded in the cytosolic monolayer, generating membrane tension that induces the pore, while the α9 monomer and dimer are integrated into the highly curved monolayer to reduce the line tension, thereby stabilizing and expanding the pore. 