Cellular lipids and lipid hydroperoxides (LOOH)

Cellular lipids, particularly polyunsaturated fatty acids (PUFAs) found in phospholipids, are essential components of biological membranes that maintain structural integrity and facilitate cell signaling (Dixon et al., 2012, Cell). Lipid hydroperoxides (LOOH) are the primary products of lipid peroxidation, a process where reactive oxygen species or enzymes like lipoxygenases attack these PUFAs (Gaschler & Stockwell, 2017, Biochem Biophys Res Commun). The accumulation of lipid hydroperoxides is the defining feature of ferroptosis, a form of regulated, iron-dependent cell death that is distinct from apoptosis and necrosis (Conrad & Pratt, 2019, Nat Chem Biol). In many diseases, including neurodegenerative disorders and ischemia-reperfusion injury, the excessive formation of these hydroperoxides leads to catastrophic membrane damage and cell loss (Ayala et al., 2014, Oxid Med Cell Longev). Conversely, in oncology, inducing the accumulation of lipid hydroperoxides is a promising strategy to eliminate therapy-resistant cancer cells (Stockwell et al., 2017, Cell). Therapeutic agents like radical-trapping antioxidants (RTAs) target these molecules by neutralizing lipid peroxy radicals, thereby halting the lethal peroxidation chain reaction (Zilka et al., 2017, ACS Cent Sci). Monitoring these targets often involves measuring secondary products like malondialdehyde or using fluorescent probes to detect lipid oxidation in real-time (Kagan et al., 2017, Nat Chem Biol).

Other names

Membrane lipidsPolyunsaturated fatty acidsPUFAsLipid peroxidesHydroperoxy phospholipidsReactive oxygen species products

Radical-trapping antioxidants (RTAs) and small molecules inhibit the chain reaction of lipid peroxidation by scavenging lipid peroxy radicals or by stabilizing the lipid structure against oxidative attack, thereby preventing membrane rupture and ferroptotic cell death (Conrad & Pratt, 2019, Nat Chem Biol; Zilka et al., 2017, ACS Cent Sci).