Redox regulation by sulfiredoxin-1: bridging cysteine oxidation and liver disease therapeutics

Cysteine (Cys) posttranslational modifications play a critical role in regulating protein function, cellular signaling and redox homeostasis in various physiological and pathological conditions. Sulfiredoxin-1 (SRXN1) has emerged as a key regulator of protein redox homeostasis through its involvement in Cys sulfinylation. However, the role of SRXN1 in the pathogenesis of diseases and its therapeutic implications have yet to be fully explored. Beyond its classical function in reactive oxygen species detoxification, SRXN1 also modulates redox-sensitive signaling pathways that govern inflammation, apoptosis and cell survival, making it an essential component of cellular defense against oxidative stress-related damage. Here we highlight the significance of SRXN1 in regulating Cys sulfinylation across a broad spectrum of liver diseases. Furthermore, we emphasize the critical role of SRXN1 in regulating oxidative stress and cellular signaling through its interaction and desulfinylation of target or substrate proteins, both of which are crucial to maintaining cellular function under pathological conditions. Finally, we discuss the potential therapeutic implications of targeting SRXN1 in disease contexts where oxidative stress exacerbates pathological processes. A deeper understanding of SRXN1-mediated redox regulation may offer a novel therapeutic avenue to mitigate Cys oxidation and improve clinical outcomes in various liver disease contexts.