[
Nature,
1998]
Cytochrome c leads a double life. When a cell is called on to commit apoptotic suicide, cytochrome c relocalizes from the mitochondria to the cytosol. There, it helps to activate the foot-soldiers of apoptosis - the death proteases known as caspases. How cytochrome c escapes from the mitochondria is still a matter of debate, but it is clear that certain elements within the apoptotic regulatory hierarchy do not condone such behavior. In particular, overexpression of the cell-death suppressors Bcl-2 and Bcl-xL prevents the release of cytochrome c, suggesting that these proteins act upstream of cytochrome c in the pathway to death. However, on pages 449 and 496 of this issue, Zhivotovsky et al. and Rosse et al. show that Bcl-2 can also protect cells downstream of cytochrome c release, forcing a re-evaluation of this newly acquired dogma.