ROS-dependent caspase-9 activation in hypoxic cell death

FEBS Lett. 2003 Aug 14;549(1-3):94-8. doi: 10.1016/s0014-5793(03)00795-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Caspase 9
  • Caspases / metabolism*
  • Cell Hypoxia*
  • Cell Line
  • Cell Membrane Permeability
  • Cytochromes c / metabolism
  • Enzyme Activation
  • Humans
  • Intracellular Membranes
  • Mast Cells / cytology
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure
  • Reactive Oxygen Species / metabolism*


  • Reactive Oxygen Species
  • Cytochromes c
  • CASP9 protein, human
  • Caspase 9
  • Caspases