Interplay between bax, reactive oxygen species production, and cardiolipin oxidation during apoptosis

Biochem Biophys Res Commun. 2008 Mar 28;368(1):145-50. doi: 10.1016/j.bbrc.2008.01.055. Epub 2008 Jan 22.


Bax/Bak activation and cardiolipin peroxidation are essential for cytochrome c release during apoptosis, yet, the link between them remains elusive. We report that sequence of events after exposure of mouse embryonic fibroblast (MEF) cells to actinomycin D followed the order: Bax translocation-->superoxide production-->cardiolipin peroxidation. Genetic ablation of Bax/Bak inhibited actinomycin D induced superoxide production and cardiolipin peroxidation. Rotenone caused robust superoxide generation but did not trigger cardiolipin peroxidation in Bax/Bak double knockout MEF cells. This suggests that, in addition to participating in ROS generation, Bax/Bak play another specific role in cardiolipin oxidation. In isolated mitochondria, recombinant Bax enhanced succinate induced cardiolipin oxidation and cytochrome c release. Mitochondrial peroxidase activity, likely involved in cardiolipin peroxidation, was enhanced upon incubation with recombinant Bax. Thus, cardiolipin peroxidation may be causatively and time-dependently related to Bax/Bak effects on ROS generation and peroxidase activation of cytochrome c.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Cardiolipins / metabolism*
  • Cell Line
  • Cytochromes c / metabolism
  • Dactinomycin / pharmacology
  • Fibroblasts
  • Mice
  • Mitochondria / enzymology
  • Mitochondria / metabolism
  • Oxidation-Reduction / drug effects
  • Peroxidases / metabolism
  • Protein Transport
  • Reactive Oxygen Species / metabolism*
  • Rotenone / pharmacology
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism*


  • Cardiolipins
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Rotenone
  • Dactinomycin
  • Cytochromes c
  • Peroxidases