Oxidative stress-mediated protein sulfenylation in human diseases: Past, present, and future

Reactive Oxygen Species (ROS) refer to a variety of derivatives of molecular oxygen that play crucial roles in regulating a wide range of physiological and pathological processes. Excessive ROS levels can cause oxidative stress, leading to cellular damage and even cell demise. However, moderately elevated levels of ROS can mediate the oxidative post-translational modifications (oxPTMs) of redox-sensitive proteins, thereby affecting protein functions and regulating various cellular signaling pathways. Among the oxPTMs, ROS-induced reversible protein sulfenylation represents the initial form of cysteine oxidation for sensing redox signaling. In this review, we will summarize the discovery, chemical formation, and detection approaches of protein sulfenylation. In addition, we will highlight recent findings for the roles of protein sulfenylation in various diseases, including thrombotic disorders, diabetes, cardiovascular diseases, neurodegenerative diseases, and cancer.