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Free keywords:
Animals, Apoptosis, Atomic force microscopy (AFM), Bcl-2 proteins, bcl-2-Associated X Protein, BH3 Interacting Domain Death Agonist Protein, Cardiolipins, Escherichia coli, Force spectroscopy, Gene Expression, Humans, Liposomes, Membrane, Mice, Microscopy, Atomic Force, Mitochondria, Mitochondrial Membranes, Models, Biological, Mutation, Permeability, Phosphatidylcholines, Phosphatidylethanolamines, Phosphatidylinositols, Phosphatidylserines, Protein Multimerization, Recombinant Proteins, supported lipid bilayers
Abstract:
Bcl-2 proteins are key regulators of the mitochondrial outer membrane (MOM) permeabilization that mediates apoptosis. During apoptosis, Bid is cleaved (cBid) and translocates to the MOM, where it activates Bax. Bax then oligomerizes and induces MOM permeabilization. However, little is known about how these proteins affect membrane organization aside from pore formation. In previous studies, we have shown that both cBid and Bax are able to remodel membranes and stabilize curvature. Here, we dissected the independent effects of Bax and cBid on supported lipid structures mimicking the mitochondrial composition by means of atomic force spectroscopy. We show that cBid did not permeabilize the membrane but lowered the membrane breakthrough force. On the other hand, Bax effects were dependent on its oligomeric state. Monomeric Bax did not affect the membrane properties. In contrast, oligomeric Bax lowered the breakthrough force of the membrane, which in the context of pore formation, implies a lowering of the line tension at the edge of the pore.
