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  3. A single fluorescent probe to examine the dynamics of mitochondria-lysosome interplay and extracellular vesicle role in ferroptosis

A single fluorescent probe to examine the dynamics of mitochondria-lysosome interplay and extracellular vesicle role in ferroptosis

  • Dev Cell. 2024 Jan 19:S1534-5807(24)00003-0. doi: 10.1016/j.devcel.2024.01.003.
Ling-Li Wang 1,  Yu-Zhuo Mai 1,  Ming-Hua Zheng 2,  Guang-Hai Yan 3,  Jing-Yi Jin 4
Affiliations

Affiliations

  • 1 Research Centre of Chemical Biology, Yanbian University, Yanji 133002, Jilin, China.
  • 2 Research Centre of Chemical Biology, Yanbian University, Yanji 133002, Jilin, China. Electronic address: zhengmh@ybu.edu.cn.
  • 3 Department of Anatomy, Histology, and Embryology, Jilin Key Laboratory of Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133002, Jilin, China. Electronic address: ghyan@ybu.edu.cn.
  • 4 Research Centre of Chemical Biology, Yanbian University, Yanji 133002, Jilin, China. Electronic address: jyjin-chem@ybu.edu.cn.
PMID: 38272028 DOI: 10.1016/j.devcel.2024.01.003
Abstract

Ferroptosis is a non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation and glutathione (GSH) depletion. Despite recent advances, challenges remain in understanding the bidirectional interactions or interplay between organelles during Ferroptosis. In this study, we aimed to understand the interplay between mitochondria (Mito) and lysosomes (Lyso) in cell homeostasis and Ferroptosis. For this purpose, we designed a single fluorescent probe that marks GSH in Mito and hypochlorous acid (HOCl) in Lyso with two distinct emissions. Using this dual-targeted single fluorescent probe (9-morphorino pyronine), we detected Mito-Lyso interplay in Ferroptosis. We disclosed differences in Mito-Lyso interplay depending on the induction of Ferroptosis. Although erastin treatment decreased GSH, RSL3 triggered a HOCl burst, and FIN56- and FINO2-induced Ferroptosis increased GSH and HOCl. Additionally, we showed that only extracellular vesicles generated during erastin-induced Ferroptosis could spontaneously move and DOCK to neighboring cells, resulting in accelerated cell death.

Keywords

cell imaging; extracellular vesicles; ferroptosis; fluorescent probe; mitochondria-lysosome interplay.

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