Mitochondrial calcium release induced by prooxidants

Toxicol Lett. 1993 Apr;67(1-3):119-27. doi: 10.1016/0378-4274(93)90050-8.


Hydrogen peroxide, a physiological metabolite, and a variety of other potentially toxic prooxidants, cause oxidation of the pyridine nucleotides NAD(P)H to NAD(P)+ in mitochondria. In Ca(2+)-loaded mitochondria NAD+ thus formed is hydrolyzed to ADP-ribose and nicotinamide. Subsequent to NAD+ hydrolysis, Ca2+ is released from the organelles via a specific pathway which is sensitive to several inhibitors, among them cyclosporine A and some of its derivatives. The release is probably regulated by peptidyl-prolyl cis-trans isomerase. Prolonged stimulation of the release pathway by certain prooxidants followed by re-uptake and release of Ca2+ (Ca2+ 'cycling') leads to collapse of the mitochondrial membrane potential, and is detrimental to the organelles. Excessive Ca2+ 'cycling' is likely to be a basis for the cell toxicity of some prooxidants. On the other hand, the toxicity of inhibitors of the prooxidant-induced Ca2+ release pathway may be due to long-term Ca2+ overloading of mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidants / pharmacology*
  • Oxidation-Reduction


  • Oxidants
  • Calcium