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Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

Mitochondrial release of AIF and EndoG requires caspase activation downstream of Bax/Bak-mediated permeabilization

Damien Arnoult1, Brigitte Gaume, Mariusz Karbowski

  • 1Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.

The EMBO Journal
|August 28, 2003
PubMed

Insights

Pro-apoptotic Bcl-2 proteins selectively release factors like cytochrome c but not EndoG or AIF from mitochondria. EndoG and AIF are released later, dependent on caspase activation, defining a conserved DNA degradation pathway.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitochondrial outer-membrane permeabilization is key in apoptosis.
  • The simultaneous release of all apoptogenic factors is not fully understood.

Purpose of the Study:

  • To investigate the selective release of mitochondrial apoptogenic factors.
  • To determine the role of Bcl-2 family proteins and caspases in this process.

Main Methods:

  • Experiments using cell cultures and isolated mitochondria.
  • Treatment with pro-apoptotic drugs and caspase inhibitors (zVAD-fmk).
  • Assessing the release of cytochrome c, Smac/Diablo, HtrA2/Omi, EndoG, and AIF.

Main Results:

  • Pro-apoptotic Bcl-2 proteins release cytochrome c, Smac/Diablo, and HtrA2/Omi, but not EndoG or AIF.
  • Caspase inhibition or Apaf-1 loss prevented EndoG and AIF release, but not that of other factors.
  • EndoG and AIF release is downstream of caspase activation.

Conclusions:

  • Mitochondrial response to apoptosis is selective, with hierarchical effector release.
  • EndoG and AIF define a conserved, caspase-dependent DNA degradation pathway initiated by mitochondria.

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