Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes

Abstract

Significance Bcl-2 (B-cell lymphoma 2) proteins are key regulators of apoptosis. The recruitment of the predominantly cytosolic Bcl-2 protein Bax (Bcl-2 associated X, apoptosis regulator) to the mitochondria is associated with mitochondrial outer membrane permeabilization and apoptosis. We report specific interactions between the transmembrane domains (TMDs) of Bax and the prosurvival Bcl-x L (B-cell lymphoma-extra large) and Bcl-2 proteins. Our results demonstrate that these interactions occur in nonapoptotic human cells and participate in the regulation of Bcl-2 proteins, introducing the concept of modulation mitochondrial apoptosis signaling by TMD-mediated Bcl-2 protein interactions.