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Tracking the dynamic change of mitochondrial viscosity in ferroptosis via a NIR fluorescent probe
Tao Jiang1, Tianxin Liu1, Xin Wen1
1School of Chemistry and Chemical Engineering, University of Jinan, Shandong 250022, China.
Abstract:
Ferroptosis is a regulated cell-death pathway that is tightly linked to mitochondrial impairment. Consequently, tracking variations in intramitochondrial viscosity is important for the early identification of ferroptosis-related disorders. Here, we develop a mitochondria-localized near-infrared fluorescent probe (Mito-VF), enabling in situ reporting of viscosity changes throughout ferroptosis. Mito-VF is constructed on a donor-π-acceptor (D-π-A) architecture, incorporating a thiophene-aminothiazole electron donor and a quinolinium acceptor. Owing to a twisted intramolecular charge transfer (TICT) process, the NIR emission responds of probe Mito-VF sensitively to the viscosity of the local environment. Furthermore, the probe exhibits a distinct Stokes shift and effective mitochondrial targeting, enabling high-contrast fluorescence imaging in cells. Using live-cell microscopy, we captured a progressive elevation of mitochondrial viscosity in an erastin-triggered ferroptosis model. As ferroptosis progressed, the fluorescence signals increased in a time- and concentration-dependent trend. Importantly, administration of ferrostatin-1 reversed the viscosity-associated signal, indicating that ferroptosis can be mitigated alongside the recovery of mitochondrial viscosity.
Insights
Researchers developed a novel near-infrared fluorescent probe, Mito-VF, to track changes in mitochondrial viscosity during ferroptosis. This probe enables early detection of ferroptosis-related disorders by monitoring viscosity fluctuations within mitochondria.
Area of Science:
- Biochemistry
- Cell Biology
- Medical Imaging
Background:
- Ferroptosis is a regulated cell death pathway linked to mitochondrial dysfunction.
- Monitoring intramitochondrial viscosity is crucial for early diagnosis of ferroptosis-related diseases.
Purpose of the Study:
- To develop and validate a mitochondria-targeted, near-infrared fluorescent probe (Mito-VF) for real-time monitoring of viscosity changes during ferroptosis.
- To investigate the dynamic changes in mitochondrial viscosity during ferroptosis progression.
Main Methods:
- Design and synthesis of Mito-VF based on a donor-π-acceptor (D-π-A) architecture with a thiophene-aminothiazole donor and quinolinium acceptor.
- Utilizing a twisted intramolecular charge transfer (TICT) mechanism for viscosity-sensitive near-infrared emission.
- Live-cell fluorescence microscopy to observe Mito-VF localization, mitochondrial viscosity changes, and the effect of ferroptosis inhibitors.
Main Results:
- Mito-VF demonstrated effective mitochondrial targeting and high-contrast imaging capabilities.
- The probe's fluorescence intensity increased progressively with elevated mitochondrial viscosity in an erastin-induced ferroptosis model.
- The observed viscosity changes and fluorescence signals were time- and concentration-dependent.
- Ferrostatin-1 treatment reversed the viscosity-associated signal, confirming the probe's ability to monitor ferroptosis mitigation.
Conclusions:
- Mito-VF is a valuable tool for in situ reporting of mitochondrial viscosity variations during ferroptosis.
- The developed probe facilitates the early identification and monitoring of ferroptosis-related disorders.
- Mitochondrial viscosity changes are a key indicator that can be modulated by therapeutic interventions like ferrostatin-1.
