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

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

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

  1. Paschalis-Thomas Doulias,
  2. Margarita Tenopoulou,
  3. Jennifer L. Greene,
  4. Karthik Raju*, and
  5. Harry Ischiropoulos
  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.
  1. To whom correspondence should be addressed. E-mail: ischirop{at}mail.med.upenn.edu
  • * 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.

Citation:

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

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