Lipid peroxidation in cellular and mitochondrial membranes (LPO)

Cellular and mitochondrial membranes are the primary structural sites for lipid peroxidation, a self-propagating free radical chain reaction that degrades polyunsaturated fatty acids (PUFAs). This process is initiated by reactive oxygen species (ROS) and results in the formation of lipid hydroperoxides and reactive aldehydes, such as 4-hydroxynonenal (4-HNE), which can damage proteins and DNA (Ayala et al., 2014, Oxidative Medicine and Cellular Longevity). Mitochondrial membranes are especially vulnerable due to their high concentration of cardiolipin and proximity to the electron transport chain, a major source of endogenous ROS (Murphy, 2009, Biochemical Journal). Excessive lipid peroxidation is the hallmark of ferroptosis, a regulated form of iron-dependent cell death implicated in various pathologies including neurodegeneration and acute organ failure (Dixon et al., 2012, Cell). Therapeutic strategies target this process using lipophilic radical-trapping antioxidants (RTAs) like Ferrostatin-1 or mitochondria-targeted compounds like MitoQ to prevent membrane rupture and maintain cellular homeostasis (Gaschler & Stockwell, 2017, Nature Chemical Biology). Consequently, inhibiting lipid peroxidation is a major focus in developing treatments for diseases characterized by high oxidative stress and membrane dysfunction.

Other names

Membrane lipid peroxidationMitochondrial lipid peroxidationOxidative lipid degradationPUFA peroxidation chain reactionLipid peroxidation

Radical scavenging and chain-breaking inhibition of lipid hydroperoxide formation within the lipid bilayer