ROS-dependent caspase-9 activation in hypoxic cell death |
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Authors: | Kim Jee-Youn Park Jae-Hoon |
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Affiliation: | Department of Pathology, College of Medicine, Kyung Hee University, Seoul 130-701, South Korea. |
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Abstract: | Mitochondria are known to play a fundamental role in apoptosis by releasing apoptogenic molecules such as cytochrome c into the cytoplasm, thereby sequentially activating initiator caspase-9. However, the mechanisms of cytochrome c release or caspase-9 activation in response to hypoxia are unclear. In this report, we show that caspase-9 is activated by reactive oxygen species (ROS) without involvement of cytochrome c release in hypoxic injury. In addition, activated caspase-9 induces permeability transition (PT)-independent cytochrome c release, suggesting that caspase-9 may disrupt mitochondrial diffusion limit of cytochrome c and serve to amplify further release of cytochrome c. |
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