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Updated: Jul 28, 2025

Dual-color Correlative Light and Electron Microscopy for the Visualization of Interactions between Mitochondria and Lysosomes
Published on: September 27, 2024
The rational utilization of organelle microenvironment for imaging of lysosomal SO2 with high fidelity
Caiyun Liu1, Xiwei Li1, Xiaodi Rong1
1School of Water Conservancy and Environment, University of Jinan, Jinan, 250022, China.
Abstract:
Nowadays, more and more studies have linked the abnormal expression of active molecules in organelles with the occurrence of diseases, so there is an urgent need to develop tools for detecting active molecules in specific organelles. However, the recognition receptors of most organelle-targeting probes currently developed always remain active, which easily causes them to react with the analyte in the cytoplasm, thus misjudging the role of the analyte in the physiological and pathological processes. Therefore, it is of great significance to develop a new strategy for the design of probes capable of high-fidelity imaging of the analyte in specific organelles. Herein, we propose a new strategy that the activation of recognition receptors that can be triggered by the microenvironment of targeting organelles. Based on this strategy, we develop a novel lysosome-targeting fluorescent probe (Lyso-SO2) for imaging of sulfur dioxide (SO2) with high-fidelity in lysosomes. The inert probe is activated by the acidic environment in the lysosome and then responds quickly (<2 s) and sensitively (LOD = 0.34 μM) to SO2. This paradigm by taking full advantage of the features of the organelle microenvironment provides a promising methodology for developing organelle-targeting probes for high-fidelity imaging.
Insights
Researchers developed a novel fluorescent probe for accurately detecting sulfur dioxide (SO2) within lysosomes. This new probe utilizes the lysosome's acidic environment for activation, ensuring high-fidelity imaging of SO2 in cellular processes.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Chemical Biology
Background:
- Abnormal active molecule expression in organelles is linked to diseases, necessitating organelle-specific detection tools.
- Existing organelle probes often have active recognition receptors, leading to off-target reactions and inaccurate results.
- Developing probes with high-fidelity imaging capabilities for specific organelles is crucial for understanding physiological and pathological processes.
Purpose of the Study:
- To propose a new strategy for designing organelle-targeting probes activated by the organelle's microenvironment.
- To develop a novel lysosome-targeting fluorescent probe for high-fidelity sulfur dioxide (SO2) imaging.
- To demonstrate the probe's effectiveness in accurately detecting SO2 within lysosomes.
Main Methods:
- Designed a novel lysosome-targeting fluorescent probe (Lyso-SO2) based on microenvironment-triggered activation.
- Utilized the acidic environment of lysosomes to activate the probe's recognition receptors.
- Evaluated the probe's response time and limit of detection (LOD) for SO2.
Main Results:
- The developed probe (Lyso-SO2) is activated by the acidic lysosomal microenvironment.
- The probe exhibits rapid response (<2 s) and high sensitivity (LOD = 0.34 μM) to SO2.
- Achieved high-fidelity imaging of SO2 specifically within lysosomes.
Conclusions:
- A novel strategy utilizing organelle microenvironment features for probe activation was successfully implemented.
- The Lyso-SO2 probe provides a promising tool for high-fidelity SO2 imaging in lysosomes.
- This approach offers a new methodology for developing advanced organelle-targeting probes.

