Abstract
Protein lipoxidation is a non-enzymatic post-translational modification that consists of the covalent addition of reactive lipid species to proteins. This occurs under basal conditions but increases in situations associated with oxidative stress. Protein targets for lipoxidation include metabolic and signalling enzymes, cytoskeletal proteins, and transcription factors, among others. There is strong evidence for the involvement of protein lipoxidation in disease, including atherosclerosis, neurodegeneration, and cancer. Nevertheless, the involvement of lipoxidation in cellular regulatory mechanisms is less understood. Here we review basic aspects of protein lipoxidation and discuss several features that could support its role in cell signalling, including its selectivity, reversibility, and possibilities for regulation at the levels of the generation and/or detoxification of reactive lipids. Moreover, given the great structural variety of electrophilic lipid species, protein lipoxidation can contribute to the generation of multiple structurally and functionally diverse protein species. Finally, the nature of the lipoxidised proteins and residues provides a frameshift for a complex interplay with other post-translational modifications, including redox and redox-regulated modifications, such as oxidative modifications and phosphorylation, thus strengthening the importance of detailed knowledge of this process.
Highlights
Lipids constitute a structurally and functionally heterogeneous group of hydrophobic biomolecules that, among other species, include fatty acids, triacylglycerols, phospholipids, and sterols
Lipid oxidation is a common transformation that occurs in physiological conditions as a consequence of cellular metabolism but is usually increased under conditions of oxidative stress, i.e., in situations where there is a redox imbalance potentially leading to cellular damage
The term protein lipoxidation refers to the non-enzymatic post-translational modification (PTM) of proteins by reactive or electrophilic lipid species, which frequently arise from lipid oxidation
Summary
Lipids constitute a structurally and functionally heterogeneous group of hydrophobic biomolecules that, among other species, include fatty acids, triacylglycerols, phospholipids, and sterols. Lipids can undergo various metabolic transformations, which contribute to their great structural and functional variety Among these reactions, lipid oxidation is a common transformation that occurs in physiological conditions as a consequence of cellular metabolism but is usually increased under conditions of oxidative stress, i.e., in situations where there is a redox imbalance potentially leading to cellular damage. Some oxidized lipids are or lead to the formation of reactive or electrophilic molecules that can form covalent adducts with other macromolecules, including proteins. The term protein lipoxidation refers to the non-enzymatic post-translational modification (PTM) of proteins by reactive or electrophilic lipid species, which frequently arise from lipid oxidation. Lipoproteins: particles formed by amphipathic proteins embedded in a phospholipid monolayer and surrounding an inner core of cholesterol, cholesterol esters and triacylglycerols They function as lipid transporters and are commonly found in plasma
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