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Investigating Mitochondrial Viscosity in Ferroptosis-Mediated Drug-Induced Liver Injury using a Double-Targeted
Yongqing Zhou1, Yan Wang1, Bing Huang1
1School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, P. R. China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|December 16, 2025
Summary
Researchers developed a novel near-infrared fluorescent probe (FTZ-2) to monitor mitochondrial viscosity changes in ferroptosis-mediated drug-induced liver injury (DILI). This tool aids in early diagnosis and evaluating therapeutic effects against liver injury.
Area of Science:
- Biochemistry
- Cell Biology
- Medical Diagnostics
Background:
- Mitochondrial viscosity is a crucial factor in ferroptosis-mediated drug-induced liver injury (DILI).
- Accurate monitoring of viscosity changes is challenging due to impaired mitochondrial function in DILI.
- High expression of mitochondrial uncoupling protein 2 (UCP2) is observed in liver injury.
Purpose of the Study:
- To develop a novel method for investigating mitochondrial viscosity in ferroptosis-mediated DILI.
- To introduce a mitochondrial double-targeted strategy for enhanced probe localization and selectivity.
- To evaluate the potential of a new fluorescent probe for diagnosing and assessing liver injury.
Main Methods:
- Synthesis and characterization of a new near-infrared fluorescent probe (FTZ-2).
- Development of a mitochondrial double-targeted strategy combining electrostatic reaction and probe-protein docking.
- Application of FTZ-2 to monitor viscosity variations in ferroptosis cells and DILI mouse models.
Main Results:
- The FTZ-2 probe demonstrated high selectivity for environmental viscosity.
- FTZ-2 exhibited favorable cytotoxicity and mitochondrial localization.
- Reduced fluorescence signals correlated with the alleviating effects of ferrostatin-1, glutathione, and N-acetyl-L-cysteine on liver injury.
- High expression of UCP2 was confirmed in ferroptosis and DILI mouse livers.
Conclusions:
- The developed double-targeted strategy enables effective monitoring of mitochondrial viscosity variations in DILI.
- FTZ-2 serves as a valuable tool for early diagnosis and evaluation of ferroptosis-mediated liver injury.
- This approach contributes to improving therapeutic strategies for liver injury.
Keywords:
double‐targeted strategyferroptosis‐mediated drug‐induced liver injurymitochondrial viscositynear‐infrared fluorescent probeuncoupling protein 2More Related Videos
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