Conformation of the Bax C-terminus regulates subcellular location and cell death

Abstract

Bax, a pro‐apoptotic member of the Bcl‐2 family, translocates from the cytosol to the mitochondria during programmed cell death. We report here that both gain‐of‐function and loss‐of‐function mutations can be achieved by altering a single amino acid in the Bax hydrophobic C‐terminus. The properly mutated C‐terminus of Bax can target a non‐relevant protein to the mitochondria, showing that specific conformations of this domain alone allow mitochondrial docking. These data along with N‐terminus epitope exposure experiments suggest that the C‐ and the N‐termini interact and that upon triggering of apoptosis, Bax changes conformation, exposing these two domains to insert into the mitochondria and regulate the cell death machinery.