Apoptosis

, Volume 12, Issue 5, pp 913–922 | Cite as

Mitochondria, oxidative stress and cell death

  • Martin Ott
  • Vladimir Gogvadze
  • Sten Orrenius
  • Boris Zhivotovsky
Article

Abstract

In addition to the well-established role of the mitochondria in energy metabolism, regulation of cell death has recently emerged as a second major function of these organelles. This, in turn, seems to be intimately linked to their role as the major intracellular source of reactive oxygen species (ROS), which are mainly generated at Complex I and III of the respiratory chain. Excessive ROS production can lead to oxidation of macromolecules and has been implicated in mtDNA mutations, ageing, and cell death. Mitochondria-generated ROS play an important role in the release of cytochrome c and other pro-apoptotic proteins, which can trigger caspase activation and apoptosis. Cytochrome c release occurs by a two-step process that is initiated by the dissociation of the hemoprotein from its binding to cardiolipin, which anchors it to the inner mitochondrial membrane. Oxidation of cardiolipin reduces cytochrome c binding and results in an increased level of “free” cytochrome c in the intermembrane space. Conversely, mitochondrial antioxidant enzymes protect from apoptosis. Hence, there is accumulating evidence supporting a direct link between mitochondria, oxidative stress and cell death.

Keywords

Apoptosis Cardiolipin Cell death Mitochondria Oxidative stress 

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Copyright information

© Springer Science + Business Media, LLC 2007

Authors and Affiliations

  • Martin Ott
    • 1
  • Vladimir Gogvadze
    • 1
  • Sten Orrenius
    • 1
  • Boris Zhivotovsky
    • 1
  1. 1.Institute of Environmental MedicineKarolinska InstitutetStockholmSweden

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