Glutathione homeostasis and redox-regulation by sulfhydryl groups.

Continuous control of metabolism and developmental processes is a key feature of live cells. Cysteine thiol residues of proteins are both exceptionally useful in terms of structural and regulatory aspects, but at the same time exceptionally vulnerable to oxidation. Conserved cysteines thus are highly important for the function of metabolic enzymes and for signaling processes underlying responses to environmental factors. The underlying mechanism for the central role of thiol-mediated redox control in cellular metabolism is the ability of the cysteine-thiols to reversibly change their redox state followed by changes of structural, catalytic or regulatory functions. The cellular glutathione/glutathione disulfide redox buffer is present in cells at millimolar concentrations and forms one major basis of redox homeostasis by which protein thiols can maintain their redox state or oxidized protein thiols can be reverted to their reduced state. Besides acting as redox buffer, glutathione also acts as an electron donor for both scavenging of reactive oxygen, e.g. from photosynthesis and respiration, and metabolic reactions such as reduction of hydroperoxides and lipidperoxides or sulfate assimilation. The central role of glutathione is further emphasized by its involvement in signaling processes and the crosstalk of redox signaling processes with other means of signaling including protein glutathionylation and control of transcription factors. The present review aims at highlighting the key functions of glutathione in thiol-mediated redox control and its interplay with other protein-thiol-based redox systems.