The Cys Sense: Thiol Redox Switches Mediate Life Cycles of Cellular Proteins

Protein homeostasis is an essential component of proper cellular function; however, sustaining protein health is a challenging task, especially during the aerobic lifestyle. Natural cellular oxidants may be involved in cell signaling and antibacterial defense; however, imbalanced levels can lead to protein misfolding, cell damage, and death. This merges together the processes of protein homeostasis and redox regulation. At the heart of this process are redox-regulated proteins or thiol-based switches, which carefully mediate various steps of protein homeostasis across folding, localization, quality control, and degradation pathways. In this review, we discuss the redox code of the proteostasis network, which shapes protein health during cell growth and aging. We describe the sources and types of thiol modifications and elaborate on diverse strategies of evolving antioxidant proteins in proteostasis networks during oxidative stress conditions. We also highlight the involvement of cysteines in protein degradation across varying levels, showcasing the importance of cysteine thiols in proteostasis at large. The individual examples and mechanisms raised open the door for extensive future research exploring the interplay between the redox and protein homeostasis systems. Understanding this interplay will enable us to re-write the redox code of cells and use it for biotechnological and therapeutic purposes.

Automated summary

Protein homeostasis and redox regulation are closely connected, with redox-regulated proteins or thiol-based switches at the core. Research discusses the redox code of the proteostasis network and evolving strategies of antioxidant proteins under oxidative stress conditions. The importance of cysteine in protein degradation is also highlighted.