The Kinetics of Translocation of Smac/DIABLO from the Mitochondria to the Cytosol in HeLa Cells

• Published in: The Journal of biological chemistry Vol. 277; no. 48; pp. 45715 - 45718
• Main Authors: Springs, Stacy L, Diavolitsis, Virginia M, Goodhouse, Joseph, McLendon, George L
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 29.11.2002
• Subjects: Apoptosis; Apoptosis Regulatory Proteins; Bacterial Proteins - metabolism; Carrier Proteins - metabolism; Cell Cycle; Cytochrome c Group - metabolism; Cytosol - metabolism; HeLa Cells; Humans; Intracellular Signaling Peptides and Proteins; Kinetics; Luminescent Proteins - metabolism; Mitochondria - metabolism; Mitochondrial Proteins - metabolism; Protein Transport; Recombinant Fusion Proteins - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.C200524200

Smac ( s econd m itochondrial a ctivator of c aspases) 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.