The Cellular ‘Thiolstat’ as an Emerging Potential Target of Some Plant Secondary Metabolites

Abstract

Glutathione (GSH) is quantitatively the major thiol compound in animal and plant cells and in many prokaryotes. In unstressed cells, glutathione is almost exclusively in the reduced thiol form GSH and serves to buffer the cellular redox balance against detrimental changes. Thus, it can absorb oxidative insults to the cell by being oxidized to glutathione disulfide (GSSG) and by reversibly glutathiolating –SH groups in proteins to protect them from further oxidation. Under varying oxidizing- and reducing conditions, not only GSH but many other thiol-containing molecules in cells can undergo reversible conversion between the R-SH and R-S-S-R’ forms. Targeted oxidation of –SH groups in regulatory and signalling proteins helps the cell recognize oxidative stress and sets in motion the coordinated expression of genes involved in anti-oxidative stress responses. In addition to this targeted infrastructure however, the concentrations of reduced and oxidized GSH and other thiol compounds determine the electrochemical cell potential (redox potential) and this has an indiscriminate global effect on the redox status of many cellular proteins. It is becoming increasingly recognized that the dynamic equilibrium between reduced and oxidized thiol-containing compounds in cells is an important regulator of the cell’s physiology. The proportion of oxidized to reduced thiol groups in the cell is intimately linked with the cell’s redox status and changes in this ‘thiolstat’ are monitored and linked to signal perception and transduction. This marks the thiolstat as an important target for redox active compounds, including many physiologically active secondary metabolites from plants, bacteria, fungi, and other organisms. Here, we provide an overview of how the redox environment of the cell is controlled and how selected secondary metabolites are able to affect the cellular thiolstat and we illustrate some of the known biochemical consequences for the cell of tweaking the thiolstat.