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Updated: Sep 28, 2026

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

Mitochondrial release of apoptosis-inducing factor occurs downstream of cytochrome c release in response to several

Damien Arnoult1, Philippe Parone, Jean-Claude Martinou

  • 1EMI-U 9922 Institut National de la Santé et de la Recherche Medicale (INSERM)/Université Paris 7, IFR02, AP-HP, CHU Bichat, 75018 Paris, France. ArnoultD@ninds.nih.gov

The Journal of Cell Biology
|December 18, 2002
PubMed

Insights

Bax protein triggers cytochrome c release but not apoptosis-inducing factor (AIF) release from mitochondria during apoptosis. AIF

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Proapoptotic Bcl-2 proteins, like Bax, permeabilize the mitochondrial outer membrane, a key step in apoptosis.
  • The release of mitochondrial factors, such as cytochrome c and apoptosis-inducing factor (AIF), dictates cell death pathways.

Purpose of the Study:

  • To investigate whether Bax-mediated mitochondrial outer membrane permeabilization releases both cytochrome c and AIF.
  • To elucidate the differential release mechanisms of cytochrome c and AIF during apoptosis.

Main Methods:

  • Experiments using isolated mitochondria to assess Bax-induced protein release.
  • Cellular studies involving Bax overexpression and treatment with proapoptotic drugs (staurosporine, actinomycin D) and hydrogen peroxide.
  • Analysis of protein translocation in the presence and absence of caspase inhibitors.

Main Results:

  • Bax induced the release of cytochrome c but not AIF from isolated mitochondria.
  • AIF was found to associate with the mitochondrial inner membrane, explaining its retention during outer membrane permeabilization.
  • In cells, caspase inhibitors blocked AIF translocation but not cytochrome c translocation, indicating distinct release pathways.

Conclusions:

  • Bax-mediated outer membrane permeabilization leads to cytochrome c release, initiating caspase-dependent apoptosis.
  • AIF release is a downstream event, occurring independently of caspase executioners, and its translocation is distinct from cytochrome c.
  • These findings establish a paradigm where AIF cannot substitute for caspases due to its differential release kinetics in mitochondria-dependent cell death.

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