What are caspases 3 and 7 doing upstream of the mitochondria?

Apoptosis is a cell suicide program that is initiated after cells are exposed to cytotoxic stresses including UV, IR irradiation, chemotherapeutic drugs, hypoxia, serum deprivation and TRAIL. Caspases are the central components of this process. In mammals, caspases involved in apoptotic responses are classified into two groups according to their function and structure. The first group is termed initiator caspases (caspase-2, 8, 9, 10) that contain N-terminal adapter domains which allow for auto-cleavage and activation of downstream caspases. The second group is termed effector or executioner caspases (caspase-3, 6, 7) that lack N-terminal adapter domains and are cleaved and activated by initiator caspases. Lakhani et al. (Science 2006, 311:847-51) have reported that caspase-3 and -7 regulate mitochondrial events in the apoptotic pathway. In this journal club, we summarize the results of the article and include some open questions left in the study.