Ferroptosis: Death by Lipid Peroxidation

Ferroptosis is a regulated form of cell death driven by loss of activity of the lipid repair enzyme glutathione peroxidase 4 (GPX4) and subsequent accumulation of lipid-based reactive oxygen species (ROS), particularly lipid hydroperoxides. This form of iron-dependent cell death is genetically, biochemically, and morphologically distinct from other cell death modalities, including apoptosis, unregulated necrosis, and necroptosis. Ferroptosis is regulated by specific pathways and is involved in diverse biological contexts. Here we summarize the discovery of ferroptosis, the mechanism of ferroptosis regulation, and its increasingly appreciated relevance to both normal and pathological physiology.

TrendsFerroptosis is a regulated, nonapoptotic form of cell death distinct from other cell death modalities.Loss of GPX4 activity and subsequent accumulation of lipid hydroperoxides executes ferroptosis.Diffuse large B cell lymphomas and renal cell carcinomas are particularly susceptible to GPX4-regulated ferroptosis.Inhibition of ferroptosis may represent a promising therapeutic approach for treating pathological conditions such as acute kidney injury.