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Detection and Isolation of Apoptotic Bodies to High Purity
12:17

Detection and Isolation of Apoptotic Bodies to High Purity

Published on: August 12, 2018

Splitting the apoptosome

Andrew T Ho1, Eldad Zacksenhaus

  • 1Division of Cell & Molecular Biology, Toronto General Research Institute-University Health Network, Toronto, Ontario, Canada.

Cell Cycle (Georgetown, Tex.)
|March 17, 2004
PubMed

Insights

Mitochondrial permeabilization triggers apoptosome assembly, activating caspase-9. However, new evidence shows caspase-9 can be activated independently of the mitochondria and Apaf1 in certain cells, revealing alternative apoptotic pathways.

Area of Science:

  • Cellular biology
  • Biochemistry
  • Apoptosis research

Background:

  • The intrinsic apoptotic pathway typically involves mitochondrial permeabilization and apoptosome assembly.
  • Apoptosome formation requires cytochrome c binding to Apaf1, leading to pro-caspase-9 activation.

Purpose of the Study:

  • To investigate alternative pathways for caspase-9 activation.
  • To determine if caspase-9 can be activated independently of the apoptosome and mitochondria.

Main Methods:

  • Studied caspase-9 activation in Apaf1-mutant primary myoblasts and fibroblasts.
  • Utilized stimuli known to induce mitochondrial-dependent apoptosis.

Main Results:

  • Caspase-9 activation was observed in Apaf1-mutant primary myoblasts, but not fibroblasts.
  • This activation occurred in response to stimuli typically acting via mitochondria.
  • Suggests tissue-specific, context-dependent pathways for caspase-9 activation exist.

Conclusions:

  • Apoptosomal activation of caspase-9 is not the sole route.
  • Alternative pathways can bypass Apaf1 and mitochondria for caspase-9 activation.
  • These alternative pathways are tissue and context specific.

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