Contribution of Fluorescent Probes of Ferrous Ions to Ferroptosis Study

Abstract

As its name suggests, ferroptosis is fundamentally dependent on the presence of iron. While iron is an essential nutrient for the human body, excess iron or metabolic dysfunction of iron can cause various forms of cellular damage. In ferroptosis, lipid peroxidation serves as the trigger for ferroptosis, and iron, particularly ferrous iron (Fe²⁺), plays a central role in the lipid damage. The reaction between peroxides and ferrous iron, historically known as the Fenton reaction, generates radicals that lead to cell death when they overwhelm the cellular defense mechanisms. Many ferroptosis-inducing agents function by inhibiting the protective mechanisms against damage caused by ferrous iron and lipid peroxides. Consequently, compounds that act as iron chelators or radical scavengers function as ferroptosis inhibitors. Although the relationship between peroxidized lipids and ferroptosis has been extensively studied since the discovery of ferroptosis, the roles and subcellular dynamics of ferrous iron have only recently begun to be investigated. This delay occurred because fluorescent probes capable of detecting ferrous iron were not available at the time of ferroptosis discovery. This review introduces the principles underlying the ferrous iron fluorescent probes developed by our group and presents imaging applications of these probes, including their use in ferroptosis research.

graphical abstract