Single fluorescent probe reveals glutathione-viscosity crosstalk in the endoplasmic reticulum during ferroptosis and extracellular vesicles in synergistic ferroptosis-apoptosis

• Published in: Microchemical journal 2024-12, Vol.207, p.112232, Article 112232
• Main Authors: Liu, Yan-Ping, Wang, Ling-Li, Piao, Jing-Yu, Zheng, Ming-Hua, Jin, Jing-Yi
• Format: Article
• Language: English
• Subjects: Apoptosis; Endoplasmic reticulum; Ferroptosis; Fluorescent probe; Glutathione; Viscosity
• ISSN: 0026-265X
• DOI: 10.1016/j.microc.2024.112232

[Display omitted] •A fluorescent probe with dual-emission response to glutathione (GSH) and viscosity.•The GSH-viscosity crosstalk in endoplasmic reticulum was investigated.•The FerApo bodies with varied GSH contents were found in the synergistic process. Ferroptosis is an iron-dependent cell death triggered by lipid peroxidation accumulation, representing a redox imbalance in cells. The increased knowledge of ferroptosis has led to various potential strategies to develop new cancer therapies, such as synergistic ferroptosis-apoptosis. The endoplasmic reticulum (ER) is the major hub for lipid metabolism in cells and plays a central role in lipid peroxidation. Glutathione (GSH) and viscosity levels in ER are important parameters for intracellular redox homeostasis, which remain unclear in ferroptosis and synergistic ferroptosis-apoptosis. This study developed an ER-targeting fluorescent probe (MMPY) with a dual-emission response to GSH and viscosity. Fluorescent cell imaging using MMPY revealed different GSH-viscosity crosstalk in the ER for the four ferroptosis pathways induced by erastin, RSL3, FIN56, and FINO2. GSH and viscosity changes in the ER during synergistic ferroptosis-apoptosis were also investigated. Interestingly, the new types of extracellular vesicles were observed during the synergistic process, which burdened the ER fragments with different GSH contents.