Apoptotic Caspases: Multiple or Mistaken Identities?

The mitochondrial caspase cascade was originally thought to be required for apoptotic death driven by Bak/Bax-mediated intrinsic apoptosis. It has also been ascribed several ‘non-apoptotic’ functions, including differentiation, proliferation, and cellular reprogramming. Recent work has demonstrated that, during apoptosis, the caspase cascade suppresses damage-associated molecular pattern (DAMP)-initiated production of cytokines such as type I interferon by the dying cell. The caspase cascade is not required for death to occur; instead, it shapes the immunogenic properties of the apoptotic cell. This raises questions about the role of apoptotic caspases in regulating DAMP signaling more generally, puts a new perspective on their non-apoptotic functions, and suggests that pharmacological caspase inhibitors might find new applications as antiviral or anticancer agents.