Apoptosis-Inducing Factor Translocation to Nuclei After Transient Global Ischemia

  • Can Liu
  • Armando P. Signore
  • Guodong Cao
  • Jun Chen


Global cerebral ischemia produces both acute and delayed neuronal cell death. The loss of mitochondrial membrane integrity and the subsequent release of apoptogenic factors are critical in mediating the intrinsic, or mitochondrial, neurodegenerative pathway (Fujimura et al. 1999; Sugawara et al. 1999; Cao et al. 2003). Both caspase-dependent and -independent prodeath effector pathways can be initiated by the intrinsic pathway (Graham and Chen 2001). The key signaling molecule, released by mitochondria that initiates the caspase-independent route is apoptosis-inducing factor (AIF), a mitochondrial-specific flavoprotein that normally resides in the intermembrane space. Following global ischemia, AIF is truncated by calpain, allowing it to translocate from compromised mitochondria to the nucleus, where it degrades the nuclear genome (Fig. 9.1a–f). Along with freed AIF, endonuclease G (EndoG) is also released from mitochondria and mediates early chromatinolysis in neurons (Susin et al. 1999).


Mitochondrial Permeability Transition Pore Global Ischemia Global Cerebral Ischemia Transient Focal Cerebral Ischemia Transient Global Ischemia 
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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Can Liu
    • 1
  • Armando P. Signore
    • 1
  • Guodong Cao
    • 1
  • Jun Chen
    • 1
  1. 1.Department of NeurologyUniversity of Pittsburgh School of MedicinePittsburghUSA

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