Redox signaling in cell fate: Beyond damage

This review explores the nuanced role of reactive oxygen species (ROS) in cell fate, challenging the traditional view that equates ROS with cellular damage. Through significant technological advancements in detecting localized redox states and identifying oxidized cysteines, a paradigm shift has emerged: from ROS as merely damaging agents to crucial players in redox signaling. We delve into the intricacies of redox mechanisms, which, although confined, exert profound influences on cellular physiological responses. Our analysis extends to both the positive and negative impacts of these mechanisms on cell death processes, including uncontrolled and programmed pathways. By unraveling these complex interactions, we argue against the oversimplified notion of a ‘stress response’, advocating for a more nuanced understanding of redox signaling. This review underscores the importance of localized redox states in determining cell fate, highlighting the sophistication and subtlety of ROS functions beyond mere damage. •Redox research has shifted focus from stress to signaling.•Redox state is localized, down to nanoscale subcellular domains, not global.•Reversible cysteine thiol modifications determine signaling outcomes.•Redox regulation influences cell fate, promoting both life and death.