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Updated: Aug 1, 2025

Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function
Published on: April 26, 2024
The 4-Hydroxynonenal-Protein Adducts and Their Biological Relevance: Are Some Proteins Preferred Targets?
Lidija Milkovic1, Neven Zarkovic1, Zlatko Marusic2
1Laboratory for Oxidative Stress, Division of Molecular Medicine, Ruder Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia.
Abstract:
It is well known that oxidative stress and lipid peroxidation (LPO) play a role in physiology and pathology. The most studied LPO product with pleiotropic capabilities is 4-hydroxynonenal (4-HNE). It is considered as an important mediator of cellular signaling processes and a second messenger of reactive oxygen species. The effects of 4-HNE are mainly attributed to its adduction with proteins. Whereas the Michael adducts thus formed are preferred in an order of potency of cysteine > histidine > lysine over Schiff base formation, it is not known which proteins are the preferred targets for 4-HNE under what physiological or pathological conditions. In this review, we briefly discuss the methods used to identify 4-HNE-protein adducts, the progress of mass spectrometry in deciphering the specific protein targets, and their biological relevance, focusing on the role of 4-HNE protein adducts in the adaptive response through modulation of the NRF2/KEAP1 pathway and ferroptosis.
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