Glutathione compartmentalization and its role in glutathionylation and other regulatory processes of cellular pathways

Abstract

Glutathione is considered the major non‐protein low molecular weight modulator of redox processes and the most important thiol reducing agent of the cell. The biosynthesis of glutathione occurs in the cytosol from its constituent amino acids, but this tripeptide is also present in the most important cellular districts, such as mitochondria, nucleus, and endoplasmic reticulum, thus playing a central role in several metabolic pathways and cytoprotection mechanisms. Indeed, glutathione is involved in the modulation of various cellular processes and, not by chance, it is a ubiquitous determinant for redox signaling, xenobiotic detoxification, and regulation of cell cycle and death programs. The balance between its concentration and redox state is due to a complex series of interactions between biosynthesis, utilization, degradation, and transport. All these factors are of great importance to understand the significance of cellular redox balance and its relationship with physiological responses and pathological conditions. The purpose of this review is to give an overview on glutathione cellular compartmentalization. Information on its subcellular distribution provides a deeper understanding of glutathione‐dependent processes and reflects the importance of compartmentalization in the regulation of specific cellular pathways. © 2018 BioFactors, 45(2):152–168, 2019

A Case-Control Study of Salivary Redox Homeostasis in Hypertensive Children. Can Salivary Uric Acid be a Marker of Hypertension?

“…Considering that glutathione is an important source of cellular thiols [63], these observations are confirmed by the negative correlation between the concentration of peroxynitrite and GSH in children with hypertension. This compound is also responsible for nitration of the phenolic groups of proteins (mainly tyrosine and tryptophan) [64], which can be evidenced by increased concentration of nitrotyrosine in children with hypertension, and a positive correlation between nitrotyrosine and peroxynitrite.…”

Protection of Polyphenols against Glyco-Oxidative Stress: Involvement of Glyoxalase Pathway

“…Some authors have suggested that the increase in GSH levels in flavonoid treated cells could be related to transactivation of catalytical subunit promoter of the gamma-glutamyl-cysteine synthetase [ 60 ]. GSH is involved in cellular redox regulation as it can be used as a cofactor by enzymes involved in signal transduction [ 61 , 62 ], therefore our results suggest that polyphenol-mediated regulation of GSH levels could modulate cellular response in intestinal cells. Moreover, some flavonoids behave as natural inhibitors of GlxI [ 63 ].…”

GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients

“…The relevance of glutathionylation status in redox signaling regulation was confirmed in investigations concerning glutaredoxins, as the major intracellular enzymes with deglutathionylase activity [22]. Numerous proteins involved in signaling (kinases and phosphatases), protein folding and stability, redox homeostasis, calcium homeostasis, energy metabolism and glycolysis, as well as cytoskeletal proteins, transcription factors and heat shock proteins are regulated via S-glutathionylation [43,44]. β-actin, heat shock protein 70, heat shock protein 7c and prolactin-inducible protein have been identified as targets for deglutathionylation by GSTO1-1 [22].…”