title: Nitric oxide regulates mitochondrial fatty acid metabolism through reversible protein S-nitrosylation.
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.
authors.affiliation: Children's Hospital of Philadelphia Research Institute and Departments of Pediatrics and Pharmacology, Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Paschalis-Thomas
authors.initials: PT
authors.lastname: Doulias
authors.forename: Margarita
authors.initials: M
authors.lastname: Tenopoulou
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Greene
authors.forename: Karthik
authors.initials: K
authors.lastname: Raju
authors.forename: Harry
authors.initials: H
authors.lastname: Ischiropoulos
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004734:Energy Metabolism / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism*; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000502:physiology*; D040901:Proteomics; D026403:S-Nitrosothiols / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D017931:DNA Primers; D005227:Fatty Acids; D026403:S-Nitrosothiols; D009569:Nitric Oxide; C021315:S-nitrosocysteine; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D003545:Cysteine