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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

Effects of cytochrome c on the mitochondrial apoptosis-induced channel MAC

Liang Guo1, Dawn Pietkiewicz, Evgeny V Pavlov

  • 1Dept. of Basic Sciences, College of Dentistry, New York Univ., 345 East 24th St., New York, NY 10010, USA.

American Journal of Physiology. Cell Physiology
|April 13, 2004
PubMed

Insights

Cytochrome c release during apoptosis involves the mitochondrial apoptosis-induced channel (MAC). This channel

Area of Science:

  • Cellular Biology
  • Biophysics
  • Molecular Biology

Background:

  • Cytochrome c release from mitochondria is an early event in apoptosis.
  • This release can occur without outer mitochondrial membrane permeabilization.
  • The mitochondrial apoptosis-induced channel (MAC) is implicated in this process.

Purpose of the Study:

  • To investigate the interaction between cytochrome c and the MAC.
  • To determine the role of MAC in cytochrome c release during apoptosis.
  • To characterize the biophysical properties of MAC and its modulation by cytochrome c.

Main Methods:

  • Electrophysiological recordings of MAC in FL5.12 cells.
  • Application of physiological concentrations of cytochrome c to MAC.
  • Dose- and voltage-dependence studies of MAC activity.
  • Experiments using dextran molecules of varying sizes to probe pore diameter.

Main Results:

  • Cytochrome c modulates MAC activity through Type 1 (reversible, conductance decrease, increased noise) and Type 2 (irreversible, conductance decrease) effects.
  • MAC is a heterogeneous channel with variable conductance, affected by cytochrome c in a pore size-dependent manner.
  • MAC pore diameter is sufficient for cytochrome c passage, suggesting it's the release pathway.

Conclusions:

  • MAC is a high-conductance channel in the mitochondrial outer membrane crucial for apoptosis.
  • Cytochrome c interacts with MAC, influencing its activity and facilitating its own release.
  • These findings identify MAC as the likely pore for cytochrome c release during apoptosis.

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