From Oxytosis to Ferroptosis: 10 Years of Research on Oxidative Cell Death

Over the past decade, extensive research has been dedicated to understanding oxidative cell death, specifically the transition from oxytosis to ferroptosis. Oxytosis was initially characterized in 1989 as a calcium-dependent form of nerve cell death induced by glutamate. It was associated with intracellular glutathione depletion and the inhibition of cystine uptake through system xc-, a cystine-glutamate antiporter. In 2012, the term "ferroptosis"was coined during a compound screening that aimed to selectively induce cell death in RAS-mutated cancer cells. This screening identified erastin and RSL3 as inhibitors of system xc- and glutathione peroxidase 4 (GPX4), respectively, triggering oxidative cell death. Subsequently, the term oxytosis gradually fell out of frequent usage, being replaced by ferroptosis. This editorial provides a narrative review of the significant findings, experimental models, and molecular players involved in ferroptosis, shedding light on its intricate mechanisms. Moreover, it discusses the implications of these findings in various pathological conditions, including neurodegenerative disorders, cancer, and ischemia-reperfusion disease. By summarizing the decade-long progress made in this field, the present Forum serves as a valuable resource for researchers aiming to unravel the complex mechanisms underlying oxidative cell death and explore potential therapeutic interventions. Antioxid. Redox Signal. 39, 162-165.