A Fluorescent Probe Differentiates Apoptosis from Cysteine-Deprivation Ferroptosis through Imaging of Viscosity and Lipid Droplets.

Since death is an inevitable phenomenon, exploring cell deaths holds importance. During this process, the cellular microenvironment within cells such as pH, polarity, viscosity etc alter. One such microenvironment, viscosity elevates during different cell deaths. However, demarcating cell death processes solely based on viscosity sensing is challenging. Herein, we develop a unique fluorescent probe PS-NAP after careful investigation among three analogues for efficient viscosity imaging in HeLa cells. Cationic PS-NAP, a MMP independent molecular probe, can potentially target mitochondria and map elevated mitochondrial viscosity during apoptosis, starvation and drug induced ferroptosis processes. Notably, during ferroptosis induced by cysteine deprivation, PS-NAP exclusively colocalizes in newly generated lipid droplets (LDs) instead of mitochondria. Thus, the probe has a potential for demarcating cysteine deprivation-induced ferroptosis from other cellular stresses such as apoptosis.