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

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 both the 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 a rapid response. CMP utilizes a benzopyrylium cation for HSO₃^- recognition and mitochondrial targeting. It reacts with HSO₃^-<i>via</i> 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.