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

TLDR

Apoptosis is thought to be initiated by upstream signals that activate downstream effector caspases. The authors generated mice lacking caspase 3 and caspase 7, which died immediately after birth with severe cardiac developmental defects. Loss of caspases 3 and 7 renders cells resistant to mitochondrial and death‑receptor–mediated apoptosis, preserves mitochondrial membrane potential, delays Bax translocation and cytochrome c release, and impairs AIF nuclear translocation, demonstrating that these caspases are essential mediators of mitochondrial apoptotic events.

Abstract

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.