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

The powerhouse of our cells are mitochondria who are also crucially involved in programmed cell death (apoptosis). The main regulator is the Bcl-2 protein family who controls the permeability of the mitochondrias' outer membranes. While apoptotic (killing) Bax perforates those membranes and killing cells, the anti-apoptotic (protecting) Bcl-2 membrane protein inhibits Bax activity. Many treatment-resistant tumours are enriched in this protecting Bcl-2 protein. However, the molecular basis of apoptotic regulation by those opposing Bcl-2 members remains elusive due to the lack of detailed molecular insight. Here, we will use NR on realistic membrane systems to elucidate membrane perforation activiy of Bax, followed by NR studies to unravel the molecular principles how Bcl-2 and Bax proteins recognize and neutralize each other at the membrane level; a situation found in healthy cells.