Similar to α-helical pore-forming domains of E. coli colicins and diphtherial toxin, Bax proteins form pores in the mitochondrial membrane to initiate cell death. They may embed in the cytosolic leaflet of the lipid bilayer generating tension to induce a lipid pore with radially arranged lipids forming the wall. Alternatively, they may comprise part of the pore wall. However, there is no unambiguous structural evidence for either hypothesis. Using NMR, we determine a high-resolution structure of the Bax core region that forms a dimer with the nonpolar surface covering the lipid bilayer edge and the polar surface exposed to water. Structure-guided mutations demonstrate the importance of both polar and nonpolar interactions of the protein with the lipids in Bax pore assembly and core dimer configuration. Therefore, the Bax core dimer forms part of the proteolipid pore wall to permeabilize the mitochondrial membrane. Using crosslinking, structural modeling and functional mutagenesis, we previously discovered another dimer formed by the transmembrane helical tail of Bax (1), which links the core dimer to an oligomer that encircles the pore. Thus, both the core dimer and the tail dimer would be the minimally required building blocks for an oligomeric pore. We test this hypothesis by constructing mini-Bax proteins containing only the core and the tail regions. We image the mini-Bax complexes in membranes by negative stain TEM, and compare them with the mega pores formed by whole Bax proteins. The results will guide us to new mini-Bax proteins that can form homogenous pore complexes such that their structures can be determined by Cryo-EM at high resolutions. [Work supported by grants from National Institutes of Health (R01GM062964), OCAST (HR16-026) and Presbyterian Health Foundation to J. L., and by an Institutional Development Award from the National Institute of General Medical Sciences of National Institutes of Health (P20GM103640).]