Caspases 3 and 7: Key Mediators of Mitochondrial Events of Apoptosis

• DOI: 10.1126/science.1115035
• Publication Date: 2006-02-09T21:38:32Z
• Authors: Saquib A. Lakhani; Ali Masud; Keisuke Kuida; George A. Porter; Carmen J. Booth; Wajahat Z. Mehal; Irteza Inayat; Richard A. Flavell
• Keywords: Caspase 7; Cell Nucleus; Heart Defects, Congenital; Male; Mice, Knockout; 0301 basic medicine; Caspase 3; Cell Survival; Apoptosis Inducing Factor; Cytochromes c; Apoptosis; Heart; DNA Fragmentation; Fibroblasts; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Caspases; Animals; Female; Cell Shape; Cells, Cultured

The current model of apoptosis holds that upstream signals lead to activation of downstream effector caspases. We generated mice deficient in the two effectors, caspase 3 and caspase 7, which died immediately after birth with defects in cardiac development. Fibroblasts lacking both enzymes were highly resistant to both mitochondrial and death receptor–mediated apoptosis, displayed preservation of mitochondrial membrane potential, and had defective nuclear translocation of apoptosis-inducing factor (AIF). Furthermore, the early apoptotic events of Bax translocation and cytochrome c release were also delayed. We conclude that caspases 3 and 7 are critical mediators of mitochondrial events of apoptosis.