Title: Nitric oxide regulates mitochondrial fatty acid metabolism through reversible protein S-nitrosylation.

Authors: Doulias, Paschalis-Thomas; Tenopoulou, Margarita; Greene, Jennifer L; Raju, Karthik; Ischiropoulos, Harry

Published In Sci Signal, (2013 Jan 01)

Abstract: Cysteine S-nitrosylation is a posttranslational modification by which nitric oxide regulates protein function and signaling. Studies of individual proteins have elucidated specific functional roles for S-nitrosylation, but knowledge of the extent of endogenous S-nitrosylation, the sites that are nitrosylated, and the regulatory consequences of S-nitrosylation remains limited. We used mass spectrometry-based methodologies to identify 1011 S-nitrosocysteine residues in 647 proteins in various mouse tissues. We uncovered selective S-nitrosylation of enzymes participating in glycolysis, gluconeogenesis, tricarboxylic acid cycle, and oxidative phosphorylation, indicating that this posttranslational modification may regulate metabolism and mitochondrial bioenergetics. S-nitrosylation of the liver enzyme VLCAD [very long chain acyl-coenzyme A (CoA) dehydrogenase] at Cys(238), which was absent in mice lacking endothelial nitric oxide synthase, improved its catalytic efficiency. These data implicate protein S-nitrosylation in the regulation of β-oxidation of fatty acids in mitochondria.

PubMed ID: 23281369

MeSH Terms: Acyl-CoA Dehydrogenase, Long-Chain/metabolism; Analysis of Variance; Animals; Cysteine/analogs & derivatives*; Cysteine/metabolism; DNA Primers/genetics; Energy Metabolism/physiology*; Fatty Acids/metabolism*; Liver/anatomy & histology; Liver/metabolism; Mass Spectrometry; Mice; Mitochondria/metabolism*; Mutagenesis, Site-Directed; Nitric Oxide/metabolism*; Oxidation-Reduction; Protein Processing, Post-Translational/genetics; Protein Processing, Post-Translational/physiology*; Proteomics; S-Nitrosothiols/metabolism*; Signal Transduction/genetics; Signal Transduction/physiology*