Life-or-death decisions by the Bcl-2 protein family

In response to intracellular damage and certain physiological cues, cells e nter the suicide program termed apoptosis, executed by proteases called cas pases. Commitment to apoptosis is typically governed by opposing factions o f the Bcl-2 family of cytoplasmic proteins, Initiation of the proteolytic c ascade requires assembly of certain caspase precursors on a scaffold protei n, and the Bcl-2 family determines whether this complex can form. Its pro-s urvival members can act by sequestering the scaffold protein and/or by prev enting the release of apoptogenic molecules from organelles such as mitocho ndria. Pro-apoptotic family members act as sentinels for cellular damage: c ytotoxic signals induce their translocation to the organelles where they bi nd to their pro-survival relatives, promote organelle damage and trigger ap optosis.