Figure 1.

Molecular mechanisms of the cytotoxic effect of acrolein (Acr) in smokers are realized on several levels of cell functioning. Acrolein, through direct interaction with antioxidant enzymes (primarily GSH), disrupts redox homeostasis and contributes to the generation of ROS and the necrosis/apoptosis dependent on them. The negative effect of acrolein on mitochondrial biogenesis is also of great importance to damage to lung and respiratory system cells, i.e., inhibition of the activity of respiratory chain complexes and change of metabolism to glycolysis, mtDNA damage, mitochondrial fission, which is followed by autophagy/mitophagy. Due to the effect of acrolein on cell signaling pathways and direct interaction with numerous transcription factors (the main target of NF-kB), the aldehyde has strong immunomodulatory properties (regulation of pro-inflammatory cytokines). In addition, through the control of mucin (MUC) and metalloproteinase (MMP) gene expression, acrolein is involved in mucus hypersecretion and tissue modification and degradation in lung diseases.