Author(s):Nickells RW. Variations in the rheostat model of apoptosis: what studies of retinal ganglion cell death tell us about the functions of the Bcl2 family proteins. Exp Eye Res. 2010 Jul;91(1):2-8. doi: 10.1016/j.exer.2010.03.004. Epub 2010 Mar 15. PMID 20230818
Studies of the functions of members of the Bcl2 gene family suggested that apoptosis was controlled by a rheostat in which anti-apoptotic proteins like BCL2 bound and sequestered pro-apoptotic proteins like BAX. Our current understanding of these proteins suggests that this is a simplistic model. The new rheostat model predicts that BH3-only peptides act as neutralizing ligands for the anti-apoptotic proteins, thus allowing molecules like BAX to become activated and initiate mitochondrial dysfunction – a critical step in the intrinsic apoptotic program. Studies of retinal ganglion cell apoptosis indicate that a threshold of BAX expression is required for its successful activation, which is independent of the overall concentration of anti-apoptotic proteins in these cells.