Lipid peroxidation of membrane polyunsaturated fatty acids (LPO)

Lipid peroxidation of membrane polyunsaturated fatty acids (PUFAs) is a complex biochemical process involving the oxidative degradation of lipids. It typically proceeds via a free radical chain reaction consisting of initiation, propagation, and termination stages, where reactive oxygen species (ROS) or lipoxygenases abstract hydrogen atoms from the methylene groups of PUFAs (Ayala et al., 2014, Oxid Med Cell Longev). This leads to the formation of lipid hydroperoxides and highly reactive electrophilic aldehydes, such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), which can form adducts with proteins and DNA, causing cellular dysfunction (Gaschler & Stockwell, 2017, Biochem Biophys Res Commun). The accumulation of these lipid peroxides is the defining execution step of ferroptosis, a form of iron-dependent regulated cell death (Stockwell et al., 2017, Cell). Pathologically, excessive lipid peroxidation is implicated in neurodegenerative diseases like Alzheimer's and Parkinson's, as well as atherosclerosis and ischemia-reperfusion injury (Conrad et al., 2018, Nat Chem Biol). Therapeutic strategies targeting this process include the use of radical-trapping antioxidants (RTAs) like Ferrostatin-1, iron chelators to prevent Fenton chemistry, and the activation of the glutathione-GPX4 axis to neutralize lipid hydroperoxides (Stockwell, 2022, Nat Rev Cancer).

Other names

Membrane lipid peroxidationPUFA peroxidationOxidative lipid degradationLipid peroxidation process

Radical trapping and chain-breaking antioxidant activity to prevent the propagation of lipid peroxyl radicals, iron chelation to inhibit Fenton-mediated initiation, and enzymatic reduction of lipid hydroperoxides (Stockwell et al., 2017, Cell).