| First Author | Persichini T | Year | 2005 |
| Journal | Neurosci Lett | Volume | 384 |
| Issue | 3 | Pages | 254-9 |
| PubMed ID | 15923083 | Mgi Jnum | J:99713 |
| Mgi Id | MGI:3583495 | Doi | 10.1016/j.neulet.2005.04.085 |
| Citation | Persichini T, et al. (2005) Mitochondrial type I nitric oxide synthase physically interacts with cytochrome c oxidase. Neurosci Lett 384(3):254-9 |
| abstractText | 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. |
