Reconnoitering the role of Lipid Metabolites in Ferroptosis

Abstract

Ferroptosis is a distinct form of regulated cell death driven by iron-dependent lipid peroxidation. It is different from other cell death forms like apoptosis, necrosis, and autophagy. Unlike apoptosis, ferroptosis is induced by the accumulation of reactive lipid peroxides and lacks the typical features of cell lysis. Ferroptosis is regulated through mechanisms involving iron accumulation and lipid peroxidation, primarily driven by lipoxygenases. Glutathione Peroxidase 4 (GPX4) plays a critical role by mitigating lipid hydroperoxide accumulation. The incorporation of polyunsaturated fatty acids into cellular membranes, facilitated by enzymes such as ACSL4 and LPCAT3, enhances susceptibility to ferroptosis. Ferroptosis is implicated in various pathological conditions, including cancer, neurodegenerative diseases, and ischemic injuries. This review explores the potential of lipid metabolites as ferroptosis inducers for cancer therapy. By synthesizing recent findings on the interplay between ferroptosis and lipid metabolism, this study highlights new research directions and therapeutic strategies across diverse diseases.