The kinetics of translocation of Smac/DIABLO from the mitochondria to the cytosol in HeLa cells.
Smac (second mitochondrial activator of caspases) is released from the mitochondria during apoptosis to relieve inhibition of caspases by the inhibitor of apoptosis proteins (IAPs). The release of Smac antagonizes several IAPs and assists the initiator caspase-9 and effector caspases (caspase-3, caspase-6, and caspase-7) in becoming active, ultimately leading to death of the cell. Translocation of Smac along with cytochrome c and other mitochondrial pro-apoptotic proteins represent important regulatory checkpoints for mitochondria-mediated apoptosis. Whether Smac and cytochrome c translocate by the same mechanism is not known. Here, we show that the time required for Smac efflux from the mitochondria of cells subjected to staurosporine-induced apoptosis is approximately four times longer than the time required for cytochrome c efflux. These results suggest that Smac and cytochrome c may exit the mitochondria by different pathways.
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002453:Cell Cycle; D003574:Cytochrome c Group / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008164:Luminescent Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D003574:Cytochrome c Group; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D024101:Mitochondrial Proteins; D011993:Recombinant Fusion Proteins; C054562:yellow fluorescent protein, Bacteria