Lipid Peroxidation Mechanisms in Biological Systems
Summary
Lipid peroxidation represents a cascade of oxidative reactions targeting polyunsaturated lipids within cellular membranes and lipoprotein particles. Initiated by reactive oxygen species or transition-metal-catalysed radicals, the process proceeds through hydrogen abstraction, radical propagation and the formation of lipid hydroperoxides. These hydroperoxides can further decompose into secondary electrophilic aldehydes and ketones, which modify proteins, nucleic acids and other biomolecules. In physiological contexts, controlled lipid peroxidation underpins redox signalling and homeostatic adaptation, whereas excessive peroxidation contributes to membrane destabilisation, inflammation and cell death. Prominent among regulated outcomes is ferroptosis, a form of iron-dependent cell death driven by accumulation of lipid peroxides when glutathione peroxidase 4 activity is compromised. Cellular antioxidant systems—including enzymatic reduction of hydroperoxides and radical-scavenging small molecules—act to terminate chain reactions and restore membrane integrity. Advances in mass spectrometry, fluorescence probes and spin-trapping techniques have deepened understanding of intermediate radical species, peroxidative turnover and subcellular trafficking of oxidised lipids. This body of research informs the development of novel biomarkers for oxidative stress, antioxidant therapies in degenerative disease and strategies to modulate peroxidation in cancer and neurodegeneration.
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Lipid Peroxidation Mechanisms in Biological Systems publication trend
The graph below shows the total number of articles in lipid peroxidation mechanisms in biological systems across all publications each year (not limited to Nature Index journals).
Technical terms
Lipid peroxidation: Oxidative degradation of lipids, leading to chain reactions and formation of lipid hydroperoxides and secondary aldehydes.
Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen, including free radicals and peroxides, that initiate oxidative processes.
Hydroperoxide: A primary product of radical-mediated lipid oxidation, consisting of a peroxide group attached to a lipid backbone.
Ferroptosis: An iron-dependent form of regulated cell death caused by uncontrolled lipid peroxidation and loss of glutathione peroxidase 4 activity.
Polyunsaturated fatty acid (PUFA): Fatty acids containing more than one double bond, which are particularly susceptible to peroxidative attack.
References
- Lipid peroxidation in cell death. Biochemical and Biophysical Research Communications (2017).
- Lipid hydroperoxide generation, turnover, and effector action in biological systems. Journal of Lipid Research (1998).
- Ferroptosis: regulated cell death. Archives of Industrial Hygiene and Toxicology (2020).
- An Advanced Electron Spin Resonance (ESR) Spin-Trapping and LC/(ESR)/MS Technique for the Study of Lipid Peroxidation. International Journal of Molecular Sciences (2012).
- Hydroxycinnamyl Derived BODIPY as a Lipophilic Fluorescence Probe for Peroxyl Radicals. Antioxidants (2020).
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