title: Proteome-wide identification and quantification of S-glutathionylation targets in mouse liver.
abstract: Protein S-glutathionylation is a reversible post-translational modification regulating sulfhydryl homeostasis. However, little is known about the proteins and pathways regulated by S-glutathionylation in whole organisms and current approaches lack the sensitivity to examine this modification under basal conditions. We now report the quantification and identification of S-glutathionylated proteins from animal tissue, using a highly sensitive methodology combining high-accuracy proteomics with tandem mass tagging to provide precise, extensive coverage of S-glutathionylated targets in mouse liver. Critically, we show significant enrichment of S-glutathionylated mitochondrial and Krebs cycle proteins, identifying that S-glutathionylation is heavily involved in energy metabolism processes in vivo. Furthermore, using mice nulled for GST Pi (GSTP) we address the potential for S-glutathionylation to be mediated enzymatically. The data demonstrate the impact of S-glutathionylation in cellular homeostasis, particularly in relation to energy regulation and is of significant interest for those wishing to examine S-glutathionylation in an animal model.
authors.affiliation: Molecular Pharmacology Group, Medical Research Institute, Level 9, Jacqui Wood Cancer Centre, Dundee DD1 9SY, U.K. d.mcgarry@dundee.ac.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: McGarry
authors.affiliation: FingerPrints Proteomics Facility, MSI/WTB/JBC Complex, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
authors.forename: Wenzhang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Bioinformatics & Biostatistics Group, Cancer Research UK London Research Institute, 44, Lincoln's Inn Fields, London WC2A 3PX, U.K.
authors.forename: Probir
authors.initials: P
authors.lastname: Chakravarty
authors.affiliation: FingerPrints Proteomics Facility, MSI/WTB/JBC Complex, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Lamont
authors.affiliation: Molecular Pharmacology Group, Medical Research Institute, Level 9, Jacqui Wood Cancer Centre, Dundee DD1 9SY, U.K.
authors.forename: C Roland
authors.initials: CR
authors.lastname: Wolf
authors.affiliation: Molecular Pharmacology Group, Medical Research Institute, Level 9, Jacqui Wood Cancer Centre, Dundee DD1 9SY, U.K.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Henderson
mesh_terms: D000818:Animals; D005978:Glutathione / Q000235:genetics / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000235:genetics / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D020543:Proteome; D005982:Glutathione Transferase; D005978:Glutathione
keywords: S-glutathionylation; energy metabolism; glutaredoxin; glutathione S-transferase (Pi); liver; tandem mass tagging