Proteome-wide identification and quantification of S-glutathionylation targets in mouse liver

TY - JOUR

T1 - Proteome-wide identification and quantification of S-glutathionylation targets in mouse liver

AU - McGarry, David J.

AU - Chen, Wenzhang

AU - Chakravarty, Probir

AU - Lamont, Douglas L.

AU - Wolf, C. Roland

AU - Henderson, Colin J.

PY - 2015/6

Y1 - 2015/6

N2 - 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 glutathione S-transferase 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.

AB - 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 glutathione S-transferase 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.

U2 - 10.1042/BJ20141256

DO - 10.1042/BJ20141256

M3 - Article

C2 - 25891661

SN - 0264-6021

VL - 469

SP - 25

EP - 32

JO - Biochemical Journal

JF - Biochemical Journal

IS - 1

ER -