The Interplay of apoptosis regulating Bcl-2 proteins at mitochondrial membranes

Programmed cell death (apoptosis) is essential for human life. Its intrinsic (mitochondrial) pathway is tightly regulated by pro- and anti-apoptotic members of the Bcl-2 protein family which meet at the mitochondrial outer membrane (MOM) to control its integrity. Upon activation apoptotic proteins such as Bax perforate the MOM causing cell death. To prevent this mechanism in healthy cells anti-apoptotic proteins such as the Bcl-2 membrane protein itself reside in the MOM and inhibit Bax there. Any imbalance can cause disorder like cancer, where often overexpression of the life-guarding Bcl-2 protein ensures their survival and treatment resistance. Here, we aim to use neutron reflectometry to provide a detailed molecular and kinetic insight into the functioning of Bcl-2 by recognising and sequestering Bax at the membrane, a process to keep healthy cells and remove dysfunctional ones.