Lipid peroxidation and related lipid metabolism processes (LPO)

Lipid peroxidation and related lipid metabolism processes involve the oxidative degradation of lipids, specifically polyunsaturated fatty acids (PUFAs), within cellular membranes. This biochemical cascade is initiated by reactive oxygen species (ROS) and is significantly influenced by iron availability, leading to the formation of lipid hydroperoxides and reactive aldehydes like malondialdehyde [Ayala et al., 2014, PubMed: 24903214]. These processes are central to ferroptosis, a regulated form of cell death that is distinct from apoptosis and necrosis and is characterized by the iron-dependent accumulation of lipid peroxides [Stockwell et al., 2017, PubMed: 28985560]. In healthy cells, enzymes such as Glutathione Peroxidase 4 (GPX4) maintain membrane integrity by reducing lipid hydroperoxides to non-toxic lipid alcohols using glutathione as a cofactor [Yang et al., 2014, PubMed: 24439385]. Pathological acceleration of lipid peroxidation is a key driver in neurodegenerative diseases like Alzheimer's and Parkinson's, as well as atherosclerosis and organ ischemia-reperfusion injury. Conversely, the induction of lipid peroxidation is an emerging therapeutic strategy in oncology to eliminate therapy-resistant or mesenchymal-state cancer cells. Pharmacological intervention typically targets the enzymes regulating PUFA metabolism, such as ACSL4, or employs lipophilic antioxidants to quench chain-propagating radicals.

Other names

Lipid peroxidationOxidative lipid degradationFerroptosis-related lipid metabolismPolyunsaturated fatty acid oxidation

Modulation of lipid peroxidation occurs through the scavenging of lipid peroxyl radicals, inhibition of iron-dependent radical generation, or the direct inhibition/activation of regulatory enzymes such as Glutathione Peroxidase 4 (GPX4) and Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) [Dixon et al., 2012, PubMed: 22624694].