Reductive cell death: the other side of the coin

The balance between oxidants and antioxidants within cells, known as redox homeostasis, is crucial for proper cellular function. Disruption of redox homeostasis has been implicated in the development and treatment of various human diseases, including cancer. Regulated cell death, a fundamental biological process, occurs in various forms and functions, often caused by oxidative stress damaging macromolecules (such as DNA, lipids, and proteins). Surprisingly, recent studies have suggested that aberrant reductive stress can also trigger regulated cell death (such as disulfidptosis and pyroptosis) in cancer and immune cells, which we collectively refer to as reductive cell death. Disulfidptosis is caused by disulfide stress-induced actin cytoskeleton dysfunction, while pyroptosis is triggered by inflammasome activation. Further exploring the relationship between oxidative and reductive cell death could lead to new treatments for diseases.