Does the redox status of cytochrome C act as a fail-safe mechanism in the regulation of programmed cell death?

Free Radic Biol Med. 2001 Sep 1;31(5):697-703. doi: 10.1016/s0891-5849(01)00646-3.

Abstract

It has now become recognized that one of the key events in the induction of apoptosis, or programmed cell death, in both plants and animals is the release of cytochrome c from mitochondria. It is also known that oxidative stress imposed on cells can have a profound effect on the onset or progression of apoptosis. Here, we discuss how the redox status of cytochrome c, and thus its structure, can be altered by the presence of reactive oxygen species (ROS) and reduced glutathione (GSH). We suggest that cytochrome c will only induce programmed cell death if present in the cytoplasm in the oxidized state, and that the presence of high levels of cytoplasmic GSH maintain cytochrome c in an inactive (reduced) state, thus behaving as a fail-safe mechanism if cytochrome c is released by mitochondria when programmed cell death is not the required outcome. If the redox status of the cell is disturbed however, perhaps in the presence of hydrogen peroxide, GSH concentrations will drop, the cellular E(h) will rise, and cytochrome c will tend towards the oxidized state, allowing programmed cell death to proceed. Therefore, we propose that the redox state of cytoplasmic cytochrome c may be a key regulator of programmed cell death.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cell Line
  • Cytochrome c Group / metabolism*
  • DNA Fragmentation / physiology*
  • Ferric Compounds / metabolism*
  • Ferrous Compounds / metabolism*
  • Glutathione / metabolism
  • Humans
  • Hydrogen Peroxide / metabolism
  • Mitochondria / metabolism*
  • NADPH Oxidases / metabolism
  • Oxidation-Reduction*
  • Reactive Oxygen Species / metabolism*

Substances

  • Cytochrome c Group
  • Ferric Compounds
  • Ferrous Compounds
  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • NADPH Oxidases
  • Glutathione