"Life is nothing but an electron looking for a place to rest" - Albert Szent-Györgyi

It is now appreciated that cells contain an entire redoxome which is required modulate protein function in response to changes in cellular redox environment. This is referred to as redox signaling where changes in the redox status of cellular environments due to fluctuations in metabolism and ROS production are sensed by cysteine switches on proteins (Figure 1). Mitochondria are especially important sites for modulation by redox switches considering that mitochondrial function depends on electron movement, are a major source of cellular ROS, and contain a number of solvent accessible cysteine switches. Protein cysteine thiols can be subjected to a diverse array of oxidation events including interations with H2O2 (sulfenylation), S-nitrosylation, sulfenamide formation, and many others. However, protein S-glutathionylation (PGlu) seems to dominate mitochondrial environments since these reactions, which involve conjugating GSH to a cysteine, are enzymatically mediated, site specific, and highly sensitive to robust changes in redox environment (mediated through GSH/GSSG) (Figure 1). Various mitochondrial enzymes and proteins involved in Krebs cycle metabolism, OXPHOS, mitochondrial shape, and mitoptosis are targeted by PGlu.

Figure 1: Mitochondrial redox signaling and the control of protein function by protein S-glutathionylation (PGlu)

Our main research focus is to delineate the function of PGlu reactions in controlling mitochondrial bioenergetics, which includes identifying how PGlu can modulate ROS production. Secondly, our research goal is to examine the role mitochondrial PGlu plays in physiology and pathology, with special focus on heart disease.

The aim is to fully characterize these pathways and explore their function in controlling mitochondrial bioenergetics in cardiac tissues and other organs. Understanding how PGlu reactions control mitochondria may help unravel the importance of redox reactions in health and disease and also provide a fundamental understanding of how redox sensing has been integrated into the daily routines of cells.