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Sci. Signal., 1 January 2013
Vol. 6, Issue 256, p. rs1
[DOI: 10.1126/scisignal.2003252]

RESEARCH RESOURCES

Nitric Oxide Regulates Mitochondrial Fatty Acid Metabolism Through Reversible Protein S-Nitrosylation

Paschalis-Thomas Doulias, Margarita Tenopoulou, Jennifer L. Greene, Karthik Raju*, and Harry Ischiropoulos{dagger}

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.

* Present address: Neuroscience Graduate Group, 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 Cys238, 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.

{dagger} To whom correspondence should be addressed. E-mail: ischirop{at}mail.med.upenn.edu

Citation: P.-T. Doulias, M. Tenopoulou, J. L. Greene, K. Raju, H. Ischiropoulos, Nitric Oxide Regulates Mitochondrial Fatty Acid Metabolism Through Reversible Protein S-Nitrosylation. Sci. Signal. 6, rs1 (2013).

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Protein Microarray Characterization of the S-Nitrosoproteome.
Y.-I. Lee, D. Giovinazzo, H. C. Kang, Y. Lee, J. S. Jeong, P.-T. Doulias, Z. Xie, J. Hu, M. Ghasemi, H. Ischiropoulos, et al. (2014)
Mol. Cell. Proteomics 13, 63-72
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Regulation of Protein Function and Signaling by Reversible Cysteine S-Nitrosylation.
N. Gould, P.-T. Doulias, M. Tenopoulou, K. Raju, and H. Ischiropoulos (2013)
J. Biol. Chem. 288, 26473-26479
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