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A structural view of mitochondria-mediated apoptosis

Nature Structural Biology volume 8, pages 394–401 (2001)Cite this article

Abstract

Mitochondria-mediated apoptosis plays a central role in animal development and tissue homeostasis, and its alteration results in a range of malignant disorders including cancer. Upon apoptotic stimuli, the mitochondrial proteins cytochrome c and Smac/DIABLO are released into the cytosol, where they synergistically activate caspases by activating Apaf-1 and relieving the apoptotic inhibition by IAPs. Recent biochemical and structural studies reveal a molecular basis for these important events and identify an evolutionarily conserved mechanism of apoptosis from fruit flies to mammals.

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Figure 1: Conserved apoptotic paradigms in C. elegans, Drosophia, and mammals.
Figure 2: Recruitment of procaspase-9 by Apaf-1 through CARD–CARD interactions.
Figure 3: Smac function and a conserved IAP-binding motif.
Figure 4: Inhibition of caspases by IAP and p35.
Figure 5: Regulation of mitochondria permeability by the Bcl-2 family members.

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Acknowledgements

The author thanks B. Hay, D. Xue, and F. Hughson for critically reading the manuscript, members of the Shi laboratory for discussions, N. Hunt for secretarial assistance, and H. Wu and B. Vogelstein for sharing manuscripts before publication. The author wishes to apologize to those colleagues whose work is not cited here due to space limitations.

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  1. Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, 08544, New Jersey, USA

    Yigong Shi

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Shi, Y. A structural view of mitochondria-mediated apoptosis. Nat Struct Mol Biol 8, 394–401 (2001). https://doi.org/10.1038/87548

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