Redox mechanisms of cytoprotection by Bcl-2.

Bcl-2 is a multifunctional protein that protects against cell death induced by a wide variety of stimuli. The best characterized antiapoptotic Bcl-2 mechanism of action involves direct binding to proapoptotic proteins, e.g., Bax, inhibiting their ability to oligomerize and form pores in the mitochondrial outer membrane, through which soluble mitochondrial proapoptotic proteins, e.g., cytochrome c, are released into the cytosol. Bcl-2 also exerts antiapoptotic and antinecrotic effects that are mediated by its influence on cellular redox state and apparently independent of its interaction with proapoptotic proteins. Bcl-2 expression increases cell resistance to oxidants, augments the expression of intracellular defenses against reactive oxygen species, and may affect mitochondrial generation of superoxide radicals and hydrogen peroxide. This review focuses on the protective effects of Bcl-2 related to changes in mitochondrial redox capacity.