Identification of S-nitroso-CoA reductases that regulate protein S-nitrosylation.

Journal Article (Journal Article)

Coenzyme A (CoA) mediates thiol-based acyl-group transfer (acetylation and palmitoylation). However, a role for CoA in the thiol-based transfer of NO groups (S-nitrosylation) has not been considered. Here we describe protein S-nitrosylation in yeast (heretofore unknown) that is mediated by S-nitroso-CoA (SNO-CoA). We identify a specific SNO-CoA reductase encoded by the alcohol dehydrogenase 6 (ADH6) gene and show that deletion of ADH6 increases cellular S-nitrosylation and alters CoA metabolism. Further, we report that Adh6, acting as a selective SNO-CoA reductase, protects acetoacetyl-CoA thiolase from inhibitory S-nitrosylation and thereby affects sterol biosynthesis. Thus, Adh6-regulated, SNO-CoA-mediated protein S-nitrosylation provides a regulatory mechanism paralleling protein acetylation. We also find that SNO-CoA reductases are present from bacteria to mammals, and we identify aldo-keto reductase 1A1 as the mammalian functional analog of Adh6. Our studies reveal a novel functional class of enzymes that regulate protein S-nitrosylation from yeast to mammals and suggest that SNO-CoA-mediated S-nitrosylation may subserve metabolic regulation.

Full Text

Duke Authors

Cited Authors

  • Anand, P; Hausladen, A; Wang, Y-J; Zhang, G-F; Stomberski, C; Brunengraber, H; Hess, DT; Stamler, JS

Published Date

  • December 30, 2014

Published In

Volume / Issue

  • 111 / 52

Start / End Page

  • 18572 - 18577

PubMed ID

  • 25512491

Pubmed Central ID

  • PMC4284529

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1417816112


  • eng

Conference Location

  • United States