Identification of S-nitroso-CoA reductases that regulate protein S-nitrosylation.
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.
Duke Scholars
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- Saccharomyces cerevisiae Proteins
- Saccharomyces cerevisiae
- Protein Processing, Post-Translational
- Gene Deletion
- Coenzyme A
- Cattle
- Animals
- Alcohol Dehydrogenase
- Acyl Coenzyme A
- Acetyl-CoA C-Acetyltransferase
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Saccharomyces cerevisiae Proteins
- Saccharomyces cerevisiae
- Protein Processing, Post-Translational
- Gene Deletion
- Coenzyme A
- Cattle
- Animals
- Alcohol Dehydrogenase
- Acyl Coenzyme A
- Acetyl-CoA C-Acetyltransferase