Cellular macromolecules via iron-mediated free radical generation

Cellular macromolecules—such as nucleic acids, proteins, and lipids—are major targets of damage by free radicals generated through iron-mediated processes. Iron, due to its ability to cycle between Fe(II) and Fe(III) oxidation states, can catalyze the formation of highly reactive oxygen species (ROS), including hydroxyl radicals (·OH), which initiate oxidative damage in cells. This process leads to lipid peroxidation, protein oxidation, and DNA damage, resulting in various biological consequences like apoptosis, necrosis, and ferroptosis. While low levels of free radical generation play roles in signaling and defense against pathogens, overproduction leads to oxidative stress implicated in chronic diseases such as cancer, neurodegeneration, cardiovascular disease, and tissue injury following ischemia-reperfusion events.

Redox cycling between Fe(II)/Fe(III); Fenton chemistry; initiation/propagation of free radicals