Peroxynitrite formed by mitochondrial NO synthase promotes mitochondrial Ca2+ release

Free Radic Biol Med. 2000 Aug;29(3-4):343-8. doi: 10.1016/s0891-5849(00)00318-x.


Mitochondria contribute to the maintenance of the intracellular Ca2+ homeostasis by taking up and releasing the cation via separate and specific pathways. The molecular details of the release pathway are elusive but its stimulation by the cross-linking of some vicinal thiols and consequently NAD+ hydrolysis are known. Thiol cross-linking and NAD+ hydrolysis can be achieved by addition of peroxynitrite (ONOO-), the product of the reaction between superoxide (O2-) and nitric oxide (nitrogen monoxide, NO*) to mitochondria. Mitochondria contain an NO synthase (mtNOS), which is stimulated by Ca2+, and are a copious source of O2-. We show here that intramitochondrially formed ONOO- stimulates the specific, NAD+-linked Ca2+ release from mitochondria. Our findings that upon Ca2+ uptake mtNOS is stimulated, that ONOO- is formed, and that Ca2+ is subsequently released from intact mitochondria suggest the existence of a feedback loop, which prevents overloading of mitochondria with Ca2+.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Feedback
  • Female
  • Free Radical Scavengers / pharmacology
  • Free Radicals / antagonists & inhibitors
  • Free Radicals / metabolism
  • Homeostasis / drug effects
  • Membrane Potentials / drug effects
  • Metalloporphyrins / pharmacology
  • Mitochondria, Liver / drug effects
  • Mitochondria, Liver / enzymology
  • Mitochondria, Liver / metabolism*
  • NAD / metabolism
  • Nitrates / metabolism*
  • Nitrates / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism*
  • Oxidants / metabolism
  • Oxidants / pharmacology
  • Oxidation-Reduction / drug effects
  • Rats
  • Rats, Wistar
  • Rotenone / pharmacology
  • omega-N-Methylarginine / pharmacology
  • tert-Butylhydroperoxide / pharmacology


  • Free Radical Scavengers
  • Free Radicals
  • Metalloporphyrins
  • Nitrates
  • Oxidants
  • manganese(III)-tetrakis(4-benzoic acid)porphyrin
  • Rotenone
  • NAD
  • peroxynitric acid
  • omega-N-Methylarginine
  • tert-Butylhydroperoxide
  • Nitric Oxide Synthase
  • Calcium