Bcl-w is a member of the Bcl-2 family of proteins that regulates outer mitochondrial membrane permeability (1, 2). Bcl-w is an anti-apoptotic member that prevents release of cytochrome c from the mitochondria intermembrane space into the cytosol. Bcl-w is required for normal sperm maturation (3, 4, 5). Natural Bcl-w contains a carboxyl-terminal mitochondria targeting sequence. Recombinant Bcl-w missing the mitochondrial targeting sequence maintains its ability to neutralize pro-apoptotic Bcl-2 family members. Neutralization by Bcl-w appears to be through binding the BH3 region of pro-apoptotic Bcl-2 family members. This activity does not require the mitochondrial targeting sequence.
