Portrait of a killer: the mitochondrial apoptosome emerges from the shadows.
Apoptosis (programmed cell death) is a physiological process used to eliminate superfluous, damaged, infected, or aged cells in multicellular organisms. During apoptosis the cellular architecture is dismantled from within in a highly controlled fashion. Members of the caspase family of cysteine proteases are responsible for the destructive phase of apoptosis. One major pathway to caspase activation involves the formation of a multisubunit protease activation complex called the apoptosome. The apoptosome is assembled in response to signals that provoke mitochondrial outer membrane permeabilization and the release of cytochrome c into the cytosol. Recent studies indicate that the apoptosome is a wheel-like structure consisting of seven molecules of Apaf-1 and a similar number of caspase-9 dimers. Knowledge of the structure of the apoptosome will likely lead to the design of therapeutic modulators of apoptosis.
Molecular Cell Biology Laboratory, Department of Genetics, Smurfit Institute, Trinity College, Dublin 2, Ireland.
Michelle M
MM
Hill
Colin
C
Adrain
Seamus J
SJ
Martin
D017209:Apoptosis / Q000502:physiology*; D053477:Apoptotic Protease-Activating Factor 1; D053453:Caspase 9; D020169:Caspases / Q000737:chemistry* / Q000378:metabolism*; D003574:Cytochrome c Group / Q000502:physiology*; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D019281:Dimerization; D004789:Enzyme Activation; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D003574:Cytochrome c Group; D003838:Deoxyadenine Nucleotides; D011506:Proteins; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases; C026600:2'-deoxyadenosine triphosphate