Membrane phospholipids and lipid radicals

Membrane phospholipids, particularly those containing polyunsaturated fatty acids (PUFAs) such as arachidonic acid, are critical structural components of cellular and organelle membranes. Under conditions of oxidative stress or iron-dependent catalysis, these lipids undergo peroxidation, leading to the formation of highly reactive lipid radicals (e.g., peroxyl and alkoxyl radicals). This biochemical cascade is the execution mechanism of ferroptosis, a form of regulated cell death characterized by the catastrophic collapse of membrane integrity. Therapeutic intervention focuses on the use of radical-trapping antioxidants (RTAs) that neutralize these lipid radicals to halt the chain reaction of lipid peroxidation. This target is of significant interest in treating neurodegenerative diseases, ischemia-reperfusion injury, and organ failure, as well as in oncology, where inducing lipid peroxidation can be used to kill therapy-resistant cancer cells.

Other names

Membrane lipidsPolyunsaturated fatty acids (PUFAs)Lipid peroxidesLipid hydroperoxidesLipid peroxyl radicalsLipid alkoxyl radicals

Radical-trapping antioxidants (RTAs) act by donating a hydrogen atom to lipid peroxyl radicals, thereby terminating the self-propagating chain reaction of lipid peroxidation and preventing membrane damage.