Mitochondria-targeted long-wavelength fluorescent probe for imaging sulfur dioxide in ferroptosis

Abstract

Ferroptosis, an iron-dependent, lipid peroxidation-mediated type of programmed cell death, is crucial in the pathogenesis of numerous diseases. Mitochondria, central to cellular energy production, are significantly involved in ferroptosis. Sulfur dioxide (SO2) is generated within mitochondria and cytoplasm, and its abnormal levels are linked to mitochondrial dysfunction and various diseases. To detect mitochondrial HSO3- in ferroptosis, we developed CMP, a long-wavelength fluorescent probe with high specificity and rapid response. CMP utilizes a benzopyrylium cation for HSO3- recognition and mitochondrial targeting. It reacts with HSO3- via Michael addition, quenching fluorescence at 622 nm, and achieves ultrasensitive detection. CMP enables real-time HSO3- monitoring in HeLa cells and zebrafish, and successfully detected increased mitochondrial HSO3- levels during Erastin-induced ferroptosis and CCCP-induced apoptosis. CMP offers a valuable tool for studying ferroptosis-related diseases.