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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
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Apoptosis propagates through the cytoplasm as trigger waves.

Xianrui Cheng1, James E Ferrell2,3

  • 1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA.

Science (New York, N.Y.)
|August 11, 2018
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Summary

Programmed cell death, or apoptosis, spreads via self-regenerating trigger waves in Xenopus egg extracts and cells. These waves, traveling at ~30 micrometers per minute, are crucial for cell signaling and tissue homeostasis.

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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Biochemistry

Background:

  • Apoptosis is programmed cell death essential for animal development and homeostasis.
  • The apoptotic network may involve positive feedback loops enabling self-regenerating trigger waves.
  • Understanding these mechanisms is key to cellular signaling.

Purpose of the Study:

  • To investigate if apoptosis spreads via trigger waves in cell-free extracts and intact cells.
  • To identify the molecular components and feedback loops involved in wave propagation.
  • To determine the speed and characteristics of these apoptotic waves.

Main Methods:

  • Experiments using cell-free Xenopus laevis egg extracts.
  • Fractionation and inhibitor studies to identify key components.
  • Observation of surface waves in apoptotic oocytes and eggs.
  • Correlation analysis with caspase activation.

Main Results:

  • Apoptotic trigger waves were observed in Xenopus egg extracts at speeds of ~30 micrometers per minute.
  • Multiple feedback loops were implicated in wave generation.
  • Intact Xenopus oocytes and eggs showed correlated surface waves and caspase activation at similar speeds.
  • Apoptosis was demonstrated to spread via trigger waves in both systems.

Conclusions:

  • Apoptosis spreads through self-regenerating trigger waves in cell-free extracts and intact cells.
  • These waves are critical for propagating apoptosis over distances within cells.
  • Trigger waves represent a fundamental mechanism in cell signaling and biological processes.