The study investigates the roles of caspases 3 and 7 in apoptosis, focusing on their involvement in mitochondrial events. Mice deficient in both caspases (caspase 3−/−/caspase 7−/−) exhibited immediate postnatal death with cardiac developmental defects. Fibroblasts lacking both enzymes were highly resistant to mitochondrial and death receptor-mediated apoptosis, showing preserved mitochondrial membrane potential and defective nuclear translocation of apoptosis-inducing factor (AIF). Early apoptotic events, such as Bax translocation and cytochrome c release, were also delayed in these cells. The findings suggest that caspases 3 and 7 are critical mediators of mitochondrial events in apoptosis, contributing to the loss of mitochondrial membrane potential and AIF release. Additionally, the combined action of both caspases is crucial for viability, while caspase 3 plays a primary role in DNA fragmentation and morphological changes. These results highlight the central role of mitochondria in apoptosis and the importance of caspases 3 and 7 in amplifying the initial death signal.The study investigates the roles of caspases 3 and 7 in apoptosis, focusing on their involvement in mitochondrial events. Mice deficient in both caspases (caspase 3−/−/caspase 7−/−) exhibited immediate postnatal death with cardiac developmental defects. Fibroblasts lacking both enzymes were highly resistant to mitochondrial and death receptor-mediated apoptosis, showing preserved mitochondrial membrane potential and defective nuclear translocation of apoptosis-inducing factor (AIF). Early apoptotic events, such as Bax translocation and cytochrome c release, were also delayed in these cells. The findings suggest that caspases 3 and 7 are critical mediators of mitochondrial events in apoptosis, contributing to the loss of mitochondrial membrane potential and AIF release. Additionally, the combined action of both caspases is crucial for viability, while caspase 3 plays a primary role in DNA fragmentation and morphological changes. These results highlight the central role of mitochondria in apoptosis and the importance of caspases 3 and 7 in amplifying the initial death signal.