| First Author | Cepero E | Year | 2005 |
| Journal | Oncogene | Volume | 24 |
| Issue | 42 | Pages | 6354-66 |
| PubMed ID | 16007191 | Mgi Jnum | J:101762 |
| Mgi Id | MGI:3604948 | Doi | 10.1038/sj.onc.1208793 |
| Citation | Cepero E, et al. (2005) Caspase-9 and effector caspases have sequential and distinct effects on mitochondria. Oncogene 24(42):6354-66 |
| abstractText | Proapoptotic Bcl-2 family members alter mitochondrial permeability resulting in the release of apoptogenic factors that initiate a caspase cascade. These changes are well described; however, the effects of caspases on mitochondrial function are less well characterized. Here we describe the consequence of caspase-9 and effector caspase inhibition on mitochondrial physiology during intrinsic cell death. Caspase inhibition prevents the complete loss of mitochondrial membrane potential without affecting cytochrome c release. When effector caspases are inhibited, mitochondria become uncoupled and produce reactive oxygen species. Interestingly, the effector caspase-mediated depolarization of the mitochondria occurs independent of the activity of complexes I-IV of the electron transport chain. In contrast, caspase-9 inhibition prevents mitochondrial uncoupling and ROS production and allows for continued electron transport despite the release of cytochrome c. Taken together, these data suggest that activated caspase-9 prevents the accessibility of cytochrome c to complex III, resulting in the production of reactive oxygen species, and that effector caspases may depolarize mitochondria to terminate ROS production and preserve an apoptotic phenotype. |
