Covalent modification of DNA by α, β-unsaturated aldehydes derived from lipid peroxidation: Recent progress and challenges

Oxidative stress-induced lipid peroxidation (LPO) has been associated with human physiology and pathophysiology. LPO generates an array of oxidation products and among them reactive lipid aldehydes have received intensive research attentions due to their roles in modulating functions of biomolecules through covalent modification. Thus, covalent modification of DNA by these reactive lipid electrophiles has been postulated to be partially responsible for the biological roles of LPO. In this review, we summarized recent progress and challenges in studying the roles of covalent modification of DNA including nuclear and mitochondrial DNA by reactive lipid metabolites from LPO. We focused on the novel mechanistic insights into generation of lipid aldehydes from cellular membranes especially mitochondria through LPO. Recent advances in the technological front using mass spectrometry have also been highlighted in the settings of studying DNA damage caused by LPO and its biological relevance.