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- Title
Caspase-9 and effector caspases have sequential and distinct effects on mitochondria.
- Authors
Cepero, Enrique; King, Anne M; Coffey, Lane M; Perez, Rebeka G; Boise, Lawrence H
- Abstract
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.
- Publication
Oncogene, 2005, Vol 24, Issue 42, p6354
- ISSN
0950-9232
- Publication type
Journal Article
- DOI
10.1038/sj.onc.1208793