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Published on: December 10, 2016
Tracking Mutual Interactions of Mitochondria/Lysosomes/Lipid Droplets in DILI and NAFLD with a Viscosity and
Chunhua Fan1, Xionghao Xu1, Bo Zhao1
1School of Chemistry and Chemical Engineering, University of Jinan, Jinan, Shandong 250022, China.
Abstract:
Drug-induced liver injury and nonalcoholic fatty liver disease are associated with the cellular microenvironment and reactive oxygen species (ROS) levels, which are expected to influence complex and frequent interactions among multiple intracellular organelles. Two stimuli, an AND-gated lipid droplets (LDs), lysosomes, and mitochondria-targeted fluorescent probe (TPAP-Mito) was developed. The probe emits strong fluorescence by stimulation of both mitochondrial peroxynitrite (ONOO-) and polarity of LDs, or both the ONOO- and pH of lysosomes. Using a meticulously designed molecular logic gate, it is possible to achieve real-time tracking of three organelles in a synchronized manner, revealing a significant increase in their fusion frequency, mutual contacts, and interactions. This comprehensive study underscores the potential of developing innovative multifunctional, multitargeted probes, which could significantly improve early diagnosis and treatment options for related diseases.
Insights
Researchers developed a novel fluorescent probe to track interactions between lipid droplets, lysosomes, and mitochondria. This tool aids in understanding cellular changes related to liver diseases and developing new diagnostic methods.
Area of Science:
- Cell Biology
- Biochemistry
- Medical Diagnostics
Background:
- Drug-induced liver injury and nonalcoholic fatty liver disease involve cellular microenvironment changes and reactive oxygen species (ROS).
- Complex interactions among intracellular organelles like lipid droplets (LDs), lysosomes, and mitochondria are crucial in these conditions.
Purpose of the Study:
- To develop a novel fluorescent probe for simultaneous, real-time tracking of LDs, lysosomes, and mitochondria.
- To investigate the dynamic interactions between these organelles under specific cellular conditions.
Main Methods:
- Development of an AND-gated, mitochondria-targeted fluorescent probe (TPAP-Mito).
- The probe utilizes dual stimuli (peroxynitrite and LD polarity/lysosome pH) for fluorescence emission.
- Real-time synchronized tracking of three organelles using molecular logic gates.
Main Results:
- TPAP-Mito probe successfully enabled real-time monitoring of LDs, lysosomes, and mitochondria.
- A significant increase in fusion frequency, mutual contacts, and interactions among these organelles was observed.
- The probe's response correlated with specific cellular stimuli, indicating its sensitivity to microenvironmental changes.
Conclusions:
- Innovative multifunctional, multitargeted probes can effectively track organelle dynamics.
- Understanding organelle interactions offers insights into liver disease pathogenesis.
- This approach holds potential for improving early diagnosis and treatment strategies for related diseases.
