Metal ions-induced programmed cell death: how does oxidative stress regulate cell death?

In recent years, the mechanisms of ferroptosis and cuproptosis, two novel modes of cell death, have been elucidated and have attracted much attention. Ferroptosis is dependent on the metabolic disruption of iron ions and lipid peroxidation, whereas cuproptosis is closely related to intracellular accumulation of copper ions, aggregation of lipoylated proteins and damage to FeS cluster proteins. In particular, oxidative stress plays an important role in both types of cell death. During ferroptosis, the central role of oxidative stress is reflected in the overproduction of reactive oxygen species (ROS) and lipid peroxidation of the cell membrane. Recent studies have revealed that ROS can propagate over long distances across cells in the form of trigger waves, triggering large-scale ferroptosis. In embryonic development, different regional redox states can limit the long-distance propagation of ferroptosis waves, which is critical for muscle remodeling and tissue formation during development. In cuproptosis, processes such as copper ions accumulation, tricarboxylic acid (TCA) cycle blockade, and reduced level of FeS cluster proteins are closely associated with oxidative stress. In addition, there is a close link between oxidative stress and death induced by other metal ions (Ca²⁺, Zn²⁺, etc.). In this paper, we review the role of oxidative stress in ferroptosis and cuproptosis and the related research progress to provide new ideas for understanding the mechanism of cell death and the occurrence and treatment of related diseases.