The cys sense: Thiol redox switches mediate life cycles of cellular proteins

Meytal Radzinski, Tal Oppenheim, Norman Metanis, Dana Reichmann*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations


Protein homeostasis is an essential component of proper cellular function; however, sus-taining 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 antiox-idant 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.

Original languageAmerican English
Article number469
Pages (from-to)1-28
Number of pages28
Issue number3
StatePublished - Mar 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Chaperones
  • Oxidative stress
  • Protein degradation
  • Proteostasis
  • Redox-regulated proteins
  • Thiol switches


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