Dissecting caspase-2-mediated cell death: From intrinsic PIDDosome activation to chemical modulation

Caspase-2, an initiator caspase, plays a critical role in programmed cell death in response to certain cellular stresses. Its activation is facilitated by the PIDDosome, a multi-protein complex that assembles under conditions of genotoxic stress. Despite caspase-2's importance, the mechanisms through which it triggers cell death have remained unclear due to its inability to directly activate effector caspases. Recent research addresses this gap by demonstrating that caspase-2 directly processes BID, initiating the mitochondrial pathway of apoptosis.