Polyunsaturated fatty acids in cell membranes (PUFAs)

Polyunsaturated fatty acids (PUFAs) are essential structural components of the eukaryotic lipid bilayer, primarily incorporated into phospholipids such as phosphatidylethanolamine and phosphatidylcholine (Alberts et al., 2014). These molecules, characterized by having two or more double bonds in their carbon chain, are critical for maintaining membrane fluidity, permeability, and the proper orientation of transmembrane proteins. PUFAs also serve as the primary precursors for signaling molecules like prostaglandins, leukotrienes, and thromboxanes, which mediate inflammatory and immune responses (Dixon et al., 2012). In pathology, membrane PUFAs are the specific substrates for lipid peroxidation; when oxidized by reactive oxygen species or lipoxygenases, they trigger ferroptosis, a form of regulated iron-dependent cell death (Yang et al., 2016). Therapeutic strategies targeting membrane PUFAs include the use of deuterated fatty acids (e.g., RT-001) to stabilize the membrane against oxidative damage in neurodegenerative diseases or the administration of specific PUFAs to sensitize cancer cells to ferroptosis-inducing agents (Shchepinov, 2007; Conrad et al., 2018).

Other names

Membrane polyunsaturated fatty acidsPUFA-containing phospholipidsMembrane PUFAsPolyunsaturated lipids

Stabilization of the lipid bilayer against non-enzymatic lipid peroxidation via kinetic isotope effects or modulation of membrane composition to alter sensitivity to ferroptotic cell death.