Mitochondrial outer membrane permeabilization, which is a critical step in apoptosis, is initiated upon transmembrane insertion of the C-terminal α-helix (α9) of the pro-apoptotic Bcl-2 family protein BAX. The isolated α9 fragment (residues 173-192) is also competent to disrupt model membranes, and the structures of its membrane-associated oligomers are of interest in understanding the potential roles of this sequence in apoptosis. Here, we used ultrafast two-dimensional infrared (2D IR) spectroscopy, thioflavin T binding, and transmission electron microscopy to show that the synthetic BAX α9 peptide (α9p) forms amyloid aggregates in solution and on the surfaces of anionic small unilamellar vesicles (SUVs). Its inherent amyloidogenicity was predicted by sequence analysis, and 2D IR spectra reveal that SUVs modulate the β-sheet structures of the resulting amyloid species. These results contradict prior models of transmembrane α9p pores and motivate further examination of the formation or suppression of BAX amyloids in apoptosis. ### Competing Interest Statement The authors have declared no competing interest.
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