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Science 10 February 2006:
Vol. 311. no. 5762, pp. 847 - 851
DOI: 10.1126/science.1115035
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Reports

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

Saquib A. Lakhani,1,2 Ali Masud,1,2 Keisuke Kuida,6 George A. Porter, Jr.,2 Carmen J. Booth,3 Wajahat Z. Mehal,1,4 Irteza Inayat,4 Richard A. Flavell1,5*

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.

1 Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
2 Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA.
3 Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
4 Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
5 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
6 Vertex Pharmaceuticals, 130 Waverly Street, Cambridge, MA 02139, USA.

* To whom correspondence should be addressed. E-mail: richard.flavell{at}yale.edu

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