S-Glutathiolation in life and death decisions of the cell

Abstract

Reversible S-glutathiolation of specific proteins at sensitive cysteines provides a powerful mechanism for the dynamic, post-translational regulation of many cellular processes, including apoptosis. Critical in ascribing any regulatory function to S-glutathiolation is its reversibility, mainly regulated by glutaredoxins. Apoptosis is a controlled form of cell death that plays fundamental roles during embryonic development, tissue homeostasis and some diseases. Much of what happens during the demolition phase of apoptosis is orchestrated primarily by caspases, the final executioners of cell death. Recent findings support an essential role for S-glutathiolation in apoptosis, often at the level of caspases or their inactive precursors, and several studies have demonstrated the importance of glutaredoxins in protecting against apoptosis. These observations have contributed to recent advances in apoptosis research. However, the effective relevance of protein S-glutathiolation and the precise molecular targets in apoptotic signalling remain unresolved and a key challenge for future research.     

Insights into the role of reactive sulfhydryl groups of Carbonic Anhydrase III and VII during oxidative damage

Carbonic anhydrases (CAs) III and VII are two cytosolic isoforms of the α-CA family which catalyze the physiological reaction of carbon dioxide hydration to bicarbonate and proton. Despite these two enzymes share a 49% sequence identity and present a very similar three-dimensional structure, they show profound differences when comparing the specific activity for CO₂ hydration reaction, with CA VII being much more active than CA III. Recently, CA III and CA VII have been proposed to play a new role as scavenger enzymes in cells where oxidative damage occurs. Here, we will examine functional and structural features of these two isoforms giving insights into their newly proposed protective role against oxidative stress.     

Redox proteomics: identification and functional role of glutathionylated proteins

Although radical oxygen and nitrogen species are harmful molecules that destroy cell functions, many operate as mediators of important cell signaling pathways when not in excess. Oxidants can modify protein function through the covalent, reversible addition of glutathione to cysteine. This review addresses different proteomic methods of identifying glutathionylation targets and emphasizes ways of defining their pattern of modification in response to oxidative stimuli in cells. Finally, the literature on nonproteomic studies that investigate the functional changes induced by glutathionylation are reviewed and future studies are commented on.