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Top of Form Nature ? 2000 Nature Publishing Group Volume 407(6805)? ? ? ? ? ? ?12 October 2000? ? ? ? ? ? ?pp 770-776 The biochemistry of apoptosis [Nature Insight: Insight Review Articles] Hengartner, Michael O. Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA (e-mail: hengartn@cshl.org) Outline Abstract Caspases: the central executioners It slices, it dices, and thats not all! How to activate a caspase Processing by an upstream caspase Induced proximity Association with a regulatory subunit The handshakes that seal the fate Keep your friends close, but keep your enemies closer Mitochondria - the forum of death Bcl-2 members form channels that facilitate protein transport Bcl-2 members interact with other proteins to form channels Bcl-2 members induce rupture of the outer mitochondrial membrane Apoptotic antidotes and anti-antidotes Would apoptosis, by any other name, be as sweet a death? Conclusions Acknowledgements Graphics Box 1 Box 2 Box 3 Box 4 Box 5 Abstract Apoptosis - the regulated destruction of a cell - is a complicated process. The decision to die cannot be taken lightly, and the activity of many genes influence a cells likelihood of activating its self-destruction programme. Once the decision is taken, proper execution of the apoptotic programme requires the coordinated activation and execution of multiple subprogrammes. Here I review the basic components of the death machinery, describe how they interact to regulate apoptosis in a coordinated manner, and discuss the main pathways that are used to activate cell death.  Multicellular animals often need to get rid of cells that are in excess, in the way, or potentially dangerous. To this end, they use an active dedicated molecular programme. As important as cell division and cell migration, regulated (or programmed) cell death allows the organism to tightly control cell numbers and tissue size, and to protect itself from rogue cells that threaten homeostasis. Disco