title: Identification of S-nitroso-CoA reductases that regulate protein S-nitrosylation.
abstract: 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.
authors.affiliation: Institute for Transformative Molecular Medicine, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH 44106; Departments of Medicine and.
authors.forename: Puneet
authors.initials: P
authors.lastname: Anand
authors.affiliation: Institute for Transformative Molecular Medicine, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH 44106; Departments of Medicine and.
authors.forename: Alfred
authors.initials: A
authors.lastname: Hausladen
authors.affiliation: Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH 44106; and.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Nutrition and.
authors.forename: Guo-Fang
authors.initials: GF
authors.lastname: Zhang
authors.affiliation: Institute for Transformative Molecular Medicine, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH 44106; Departments of Medicine and.
authors.forename: Colin
authors.initials: C
authors.lastname: Stomberski
authors.affiliation: Nutrition and.
authors.forename: Henri
authors.initials: H
authors.lastname: Brunengraber
authors.affiliation: Institute for Transformative Molecular Medicine, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH 44106; Departments of Medicine and.
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Hess
authors.affiliation: Institute for Transformative Molecular Medicine, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH 44106; Departments of Medicine and Harrington Discovery Institute, University Hospitals Case Medical Center, Cleveland, OH 44106 jonathan.stamler@case.edu.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Stamler
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D000214:Acyl Coenzyme A / Q000235:genetics / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D003065:Coenzyme A / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000214:Acyl Coenzyme A; D029701:Saccharomyces cerevisiae Proteins; C010667:acetoacetyl CoA; C084625:S-nitroso-coenzyme A; D000426:Alcohol Dehydrogenase; C446927:ADH6 protein, S cerevisiae; D000101:Acetyl-CoA C-Acetyltransferase; D003065:Coenzyme A
keywords: AKR1A1; Adh6; S-nitrosylation; denitrosylase; denitrosylation