Nutritional and Metabolic Control of Ferroptosis

Ferroptosis is a type of regulated cell death characterized by an excessive lipid peroxidation of cellular membranes caused by the disruption of the antioxidant defense system and/or an imbalanced cellular metabolism. Ferroptosis differentiates from other forms of regulated cell death in that several metabolic pathways and nutritional aspects, including endogenous antioxidants (such as coenzyme Q10, vitamin E, and di/tetrahydrobiopterin), iron handling, energy sensing, selenium utilization, amino acids, and fatty acids, directly regulate the cells' sensitivity to lipid peroxidation and ferroptosis. As hallmarks of ferroptosis have been documented in a variety of diseases, including neurodegeneration, acute organ injury, and therapy-resistant tumors, the modulation of ferroptosis using pharmacological tools or by metabolic reprogramming holds great potential for the treatment of ferroptosis-associated diseases and cancer therapy. Hence, this review focuses on the regulation of ferroptosis by metabolic and nutritional cues and discusses the potential of nutritional interventions for therapy by targeting ferroptosis.

Automated summary

Ferroptosis is a regulated cell death process characterized by excessive lipid peroxidation of cellular membranes caused by disruption of the antioxidant defense system and/or imbalanced cellular metabolism. Unlike other forms of regulated cell death, the sensitivity of cells to lipid peroxidation and ferroptosis is directly regulated by various metabolic pathways and nutritional aspects. The hallmarks of ferroptosis have been observed in various diseases, making the modulation of ferroptosis a potential therapeutic approach.