Mitochondrial type I nitric oxide synthase physically interacts with cytochrome c oxidase

Tiziana Persichini, Valeria Mazzone, Fabio Polticelli, Sandra Moreno, Giorgio Venturini, Emilio Clementi, Marco Colasanti

Research output: Contribution to journalArticlepeer-review


Nitric oxide (NO) regulates key aspects of cell metabolism through reversible inhibition of cytochrome c oxidase (CcOX), the terminal electron acceptor (complex IV) of the mitochondrial respiratory chain, in competition with oxygen. Recently, a constitutive mitochondrial NOS corresponding to a neuronal NOS-I isoform (mtNOS-I) has been identified in several tissues. The role of this enzyme might be to generate NO close enough to its target without a significant overall increase in cellular NO concentrations. An effective, selective, and specific NO action might be guaranteed further by a physical interaction between mtNOS-I and CcOX. This possibility has never been investigated. Here we demonstrate that mtNOS-I is associated with CcOX, as proven by electron microscopic immunolocalization and co-immunoprecipitation studies. By affinity chromatography, we found that association is due to physical interaction of mtNOS-I with the C-terminal peptide of the Va subunit of CcOX, which displays a consensus sequence for binding to the PDZ domain of mtNOS-I previously unreported for CcOX. The molecular details of the interaction have been analyzed by means of molecular modeling and molecular dynamics simulations. This is the first evidence of a protein-protein interaction mediated by PDZ domains involving CcOX.

Original languageEnglish
Pages (from-to)254-259
Number of pages6
JournalNeuroscience Letters
Issue number3
Publication statusPublished - Aug 26 2005


  • Cytochrome c oxidase
  • Mitochondrial nitric oxide synthase
  • Neuronal nitric oxide synthase
  • Nitric oxide
  • PDZ domain

ASJC Scopus subject areas

  • Neuroscience(all)


Dive into the research topics of 'Mitochondrial type I nitric oxide synthase physically interacts with cytochrome c oxidase'. Together they form a unique fingerprint.

Cite this