First Author | Hansen TM | Year | 2006 |
Journal | Cell Death Differ | Volume | 13 |
Issue | 7 | Pages | 1181-90 |
PubMed ID | 16239929 | Mgi Jnum | J:126299 |
Mgi Id | MGI:3760962 | Doi | 10.1038/sj.cdd.4401795 |
Citation | Hansen TM, et al. (2006) Smac/DIABLO is not released from mitochondria during apoptotic signalling in cells deficient in cytochrome c. Cell Death Differ 13(7):1181-90 |
abstractText | We have characterised the apoptotic defects in cells null for cytochrome c (cyt c-/-). Such cells treated with staurosporine (STS) exhibited translocation to the mitochondria and activation of the proapoptotic signalling molecule Bax but failed to release Smac/DIABLO from these organelles, judged by both confocal microscopy and Western blotting. While reference cells expressing cytochrome c released both it and Smac/DIABLO under a variety of conditions of apoptotic induction, we have never observed release of Smac/DIABLO from cyt c-/- cells. We eliminate the possibility that proteasomal degradation of cytosolically localised Smac/DIABLO is responsible for our failure to visualise the protein outside the mitochondria. Our findings indicate an unanticipated nexus between release of cytochrome c and Smac/DIABLO from mitochondria, previously thought to be a more or less synchronised event early in apoptosis. We suggest that the failure of cyt c-/- cells to release Smac/DIABLO after recruitment of Bax to mitochondria represents an extreme manifestation of some inherent difference in the regulation of release of these two proteins from mitochondria. |