Membrane phospholipids (PL)

Membrane phospholipids, particularly those containing polyunsaturated fatty acids (PUFAs), are critical structural components of cellular and organelle membranes (NIH, 1.2.1). Under conditions of oxidative stress or iron-dependent ferroptosis, these lipids undergo a chain reaction known as lipid peroxidation, leading to the formation of toxic lipid hydroperoxides and reactive aldehydes (Frontiers, 1.1.2). This process compromises membrane permeability and leads to cell death (NIH, 1.1.1). Therapeutically, these phospholipids are targeted by radical-trapping antioxidants and ferroptosis inhibitors that prevent the propagation of the peroxidative chain (NIH, 1.4.2). Modulating lipid peroxidation is a key strategy in treating diseases characterized by excessive cell death, such as neurodegeneration and ischemia-reperfusion injury, as well as in sensitizing certain cancers to therapy (ResearchGate, 1.4.3). The accumulation of peroxidized lipids serves as a hallmark of ferroptotic cell death, distinguishing it from apoptosis and necrosis (NIH, 1.4.4). Research into this target has led to the development of specific small molecules that can halt the oxidative damage in situ within the lipid bilayer (MDPI, 1.1.4).

Other names

Polyunsaturated fatty acid-containing phospholipidsPUFA-PLsPeroxidized lipidsLipid hydroperoxidesOxidized phospholipids

Radical trapping antioxidants (RTAs) inhibit the chain reaction of lipid peroxidation by scavenging lipid peroxy radicals, thereby preventing the catastrophic breakdown of membrane integrity.