Biochemistry of mitochondrial nitric-oxide synthase

Sarah Liv Elfering, Theresa Marie Sarkela, Cecilia R Giulivi

Research output: Contribution to journalArticle

302 Scopus citations

Abstract

We reported that the generation of nitric oxide by mitochondria is catalyzed by a constitutive, mitochondrial nitric-oxide synthase (mtNOS). Given that this production may establish the basis for a novel regulatory pathway of energy metabolism, oxygen consumption, and oxygen free radical production, it becomes imperative to identify unequivocally and characterize this enzyme to provide a basis for its regulation. The mitochondrial localization of mtNOS was supported by following the hepatic distribution of mtNOS, immunoblotting submitochondrial fractions, and immunohistochemistry of liver tissues. mtNOS was identified as brain NOSα by various methods (mass spectrometry of proteolytic fragments, amino acid analysis, molecular weight, pI, and analysis of PCR fragments), excluding the occurrence of a novel isoform or other splice variants. Distribution of mtNOS transcript indicated its occurrence in liver, brain, heart, muscle, kidney, lung, testis, and spleen. In contrast to brain NOS, mtNOS has two post-translational modifications: acylation with myristic acid and phosphorylation at the C terminus. The former modification is a reversible and post-translational process, which may serve for subcellular targeting or membrane anchoring. The latter modification could be linked to enzymatic regulation. These results are discussed in terms of the role that nitric oxide may have in cellular bioenergetics.

Original languageEnglish (US)
Pages (from-to)38079-38086
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number41
DOIs
StatePublished - Oct 11 2002
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

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