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Mitochondrial apoptosis-induced channel (MAC) function triggers a Bax/Bak-dependent bystander effect

Pablo M Peixoto1, Jennifer K Lue, Shin-Young Ryu

  • 1Department of Basic Sciences, New York University College of Dentistry, New York, New York, USA.

The American Journal of Pathology
|January 13, 2011
PubMed

Insights

The bystander effect, where apoptosis spreads to nearby cells, is crucial for tissue health but hinders cancer treatments. This study reveals that the mitochondrial apoptosis-induced channel (MAC) components, Bax and Bak, are essential for this cell death signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Apoptosis, or programmed cell death, is vital for tissue homeostasis.
  • The bystander effect, collateral apoptosis spread, poses challenges for cancer therapies.
  • Mitochondrial outer membrane permeabilization, involving factors like cytochrome c, is key to apoptosis.

Purpose of the Study:

  • To investigate the role of the mitochondrial apoptosis-induced channel (MAC) in the bystander effect.
  • To determine if MAC components are essential for the spread of apoptosis to neighboring cells.

Main Methods:

  • Microinjection of cytochrome c into Xenopus laevis embryos to induce apoptosis.
  • Assessment of bystander apoptosis in mouse embryonic fibroblasts with varying expression of Bax and Bak.
  • Time-lapse microscopy to observe cell death propagation.

Main Results:

  • Cytochrome c microinjection in embryos induced apoptosis in neighboring cells, demonstrating an in vivo bystander effect.
  • Expression of Bax and/or Bak in mouse fibroblasts was essential for bystander apoptosis.
  • Cells lacking both Bax and Bak did not exhibit bystander apoptosis, even when adjacent cells underwent programmed cell death.

Conclusions:

  • The mitochondrial apoptosis-induced channel (MAC), particularly its components Bax and Bak, plays a critical role in mediating the bystander effect.
  • Understanding MAC's role in collateral apoptosis can inform the development of targeted cancer therapies and strategies to minimize tissue damage.

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