Mitochondrial Nitric-oxide Synthase: Role in Pathophysiology

Virginia Haynes, Sarah L. Elfering, Rachel J. Squires, Nathaniel Traaseth, Joseph Solien, Adam Ettl, Cecilia Giulivi

Research output: Contribution to journalReview article

Abstract

The biochemistry of the mitochondrial production of nitric oxide is reviewed to gain insight into the basic role of this radical in mitochondrial and cellular oxidative metabolism. The mitochondrial production of nitric oxide is catalyzed by a nitric-oxide synthase (mtNOS). This enzyme has the same cofactor and substrate requirements as other constitutive nitric-oxide synthases. Its occurrence was demonstrated in various mitochondrial preparations from different organs and species using diverse approaches (oxidation of oxymyoglobin, electron paramagnetic resonance in conjunction with spin trap, radiolabeled L-arginine, immunohistochemistry, nitric-oxide electrode). MtNOS has been identified as the alpha isoform of nNOS, acylated at a Thr or Ser residue, and phosphorylated at the C-terminal end. Endogenous nitric oxide reversibly inhibits oxygen consumption and ATP synthesis by competitive inhibition of cytochrome oxidase. Nitric oxide is the first molecule that fulfills the requirement for a cytochrome oxidase activity modulator: it is a competitive inhibitor, produced endogenously at a fair rate near the target site, at concentrations high enough to exhibit an inhibitory effect on cytochrome oxidase. The role of the mitochondrial nitric oxide production is discussed in terms of the physiological (modulating oxygen gradients into tissues) and pathological (abrogation of oxygen gradient modification, apoptosis, protein nitrative/oxidative stress) implications.

Original languageEnglish (US)
Pages (from-to)599-603
Number of pages5
JournalIUBMB Life
Volume55
Issue number10-11
DOIs
StatePublished - Oct 2003

Keywords

  • Free radicals
  • Mitochondria
  • Mitochondrial metabolism
  • Nitric oxide
  • Nitric-oxide synthase
  • Oxygen consumption

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Clinical Biochemistry
  • Cell Biology

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