Lipoxygenase in Ferroptosis

Cell death is indispensable for the maintenance of organic homeostasis and embryonic development under physical circumstances. Ferroptosis is a newly discovered type of cell death by Stockwell research group in 2012. It is distinct from other cell death modalities including apoptosis, necroptosis, autophagy, and pyroptosis at morphological, genetic, and biochemical levels. It is well known that ferroptotic cell death occurs through lipid peroxidation accumulation. Lipoxygenase (ALOX) serves as one of the major enzymes for the oxygenation of arachidonic acid (AA), an essential polyunsaturated fatty acid (PUFA), finally triggering lipid peroxidation and ferroptosis. Here, we make a summarization of basic knowledge of ALOX including its nomenclature, distribution in different organs, and its metabolites. Additionally, the relationship between ALOX and ferroptosis in human diseases such as neurological disorders and cancers is also discussed. We propose that ALOX may serve as a potential therapeutic target for treating multiple disorders via suppressing ferroptosis.