Speaker
Description
The elimination of unwanted cells is essential to the survival of all living organisms. This process is under the control of a set of proteins called Bcl-2 family proteins, several of which cooperate to permeabilize the outer membrane of mitochondria, sentencing the cell to death. Using reconstituted membrane systems to which we add fluorescently labelled Bcl-2 family proteins (both an activating protein, Bid, and a pore forming protein, Bax), we investigate the regulation of the pore formation process by both lipids and protein-protein interactions. Using liposomes with varying lipid compositions, we studied the influence of the physical properties of the membrane (surface charge, thickness, order parameter, spontaneous curvature) on the different steps of the Bax pore formation pathway. We found that surface charge influences the initial recruitment of Bid to the membrane, while lipid tail disorder helps the insertion of both Bid and Bax into the membrane. In addition, using a planar supported lipid bilayer and confocal imaging, we quantified the association of these two proteins directly in the membrane. Our work highlights the different layers of control that can be used by cells to regulate cell death.
