A Fluorescent Diaminoterephthalate Probe for Monitoring Lipid Droplet Dynamics and Ferroptosis in Mammalian Cells

Abstract Ferroptosis is a Fe 2+ induced programmed cell death pathway that has attracted significant attention over the last decade. It is manifested in a marked increase in the polarity of lipid droplets (LDs), as it involves lipid peroxidation. LD dynamics is affected significantly by this process. Design and choice of appropriate lipophilic fluorescent probes are crucial for monitoring these phenomena. This is the motivation for the present endeavor focused on R1, a cell permeable, lipophilic diaminoterephthalate fluorescent probe with a strongly polarity‐dependent fluorescence intensity and lifetime. Using confocal laser scanning microscopy (CLSM) and fluorescence lifetime imaging microscopy (FLIM), LD behavior in mammalian cells under ferroptosis‐inducing conditions has been observed. R1 has been found to exhibit a marked decrease in fluorescence intensity and lifetime in LDs upon treatment with erastin, thus reflecting the increased polarity brought about by ferroptosis. This sets the field for future use of R1 to investigate ferroptosis‐related processes, possibly leading to disease diagnostics and formulation of therapeutic strategies.