Formation of apoptosome is initiated by cytochrome c-induced dATP hydrolysis and subsequent nucleotide exchange on Apaf-1
Proceedings of the National Academy of Sciences, 2005•National Acad Sciences
Apoptosis in metazoans is executed by a group of intracellular proteases named caspases.
One of the caspase-activating pathways in mammals is initiated by the release of
cytochrome c from mitochondria to cytosol, where it binds to Apaf-1 to form a procaspase-9-
activating heptameric protein complex named apoptosome. We report here the
reconstitution of this pathway with purified recombinant Apaf-1, procaspase-9, procaspase-
3, and cytochrome c from horse heart. Apaf-1 contains a dATP as a cofactor. Cytochrome c …
One of the caspase-activating pathways in mammals is initiated by the release of
cytochrome c from mitochondria to cytosol, where it binds to Apaf-1 to form a procaspase-9-
activating heptameric protein complex named apoptosome. We report here the
reconstitution of this pathway with purified recombinant Apaf-1, procaspase-9, procaspase-
3, and cytochrome c from horse heart. Apaf-1 contains a dATP as a cofactor. Cytochrome c …
Apoptosis in metazoans is executed by a group of intracellular proteases named caspases. One of the caspase-activating pathways in mammals is initiated by the release of cytochrome c from mitochondria to cytosol, where it binds to Apaf-1 to form a procaspase-9-activating heptameric protein complex named apoptosome. We report here the reconstitution of this pathway with purified recombinant Apaf-1, procaspase-9, procaspase-3, and cytochrome c from horse heart. Apaf-1 contains a dATP as a cofactor. Cytochrome c binding to Apaf-1 induces hydrolysis of dATP to dADP, which is subsequently replaced by exogenous dATP. The dATP hydrolysis and exchange on Apaf-1 are two required steps for apoptosome formation.
National Acad Sciences