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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
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Caspase-2 permeabilizes the outer mitochondrial membrane and disrupts the binding of cytochrome c to anionic

Mari Enoksson1, John D Robertson, Vladimir Gogvadze

  • 1Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden.

The Journal of Biological Chemistry
|October 12, 2004
PubMed

Insights

Caspase-2 directly triggers apoptosis by permeabilizing the outer mitochondrial membrane, releasing key proteins. It also disrupts cytochrome c binding to cardiolipin, enhancing its release and promoting cell death.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Caspases are critical cysteine proteases executing apoptosis.
  • Caspase-2 activation by genotoxic stress modulates the mitochondrial apoptotic pathway.

Purpose of the Study:

  • To investigate the direct mechanism of caspase-2 in outer mitochondrial membrane permeabilization.
  • To determine if caspase-2-mediated release of cytochrome c and Smac/DIABLO is protein-dependent.

Main Methods:

  • Experiments utilized permeabilized cells, isolated mitochondria, and protein-free liposomes.
  • Assessed direct protein-phospholipid interactions and cytochrome c release.

Main Results:

  • Caspase-2 directly permeabilizes the outer mitochondrial membrane, independent of other proteins or specific phospholipids.
  • Caspase-2 disrupts cytochrome c binding to cardiolipin, enhancing its release.

Conclusions:

  • Caspase-2 directly engages the mitochondrial apoptotic pathway.
  • Caspase-2 permeabilizes the outer mitochondrial membrane and disrupts inner mitochondrial membrane interactions of cytochrome c.

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