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Sci Signal. 2013 Jan 1;6(256):rs1. doi: 10.1126/scisignal.2003252.

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

Author information

1
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.

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.

PMID:
23281369
PMCID:
PMC4010156
DOI:
10.1126/scisignal.2003252
[Indexed for MEDLINE]
Free PMC Article

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