Single Image Capture of Bioactive Ion Crosstalk within Inter-Organelle Membrane Contacts at Nanometer Resolution

Area of Science:

• Cell Biology
• Biochemistry
• Microscopy

Background:

• Rapid ion exchange is crucial for biological processes but difficult to visualize due to its speed.
• Existing super-resolution microscopy techniques face challenges in capturing these fast events.

Purpose of the Study:

• To develop a novel strategy for visualizing rapid inter-organelle ion exchange in live cells.
• To demonstrate the utility of this strategy by analyzing reactive sulfur species (RSS) at mitochondria-lysosome contact sites (MLCs).

Main Methods:

• A "converting a dynamic event into a static image construction" (CDtSC) strategy was developed.
• A dichromatic molecular probe based on coumarin-hemicyanine was designed to detect RSS with distinct colors in different organelles.
• The probe was used to visualize RSS exchange at MLCs in live cells.

Main Results:

• The CDtSC strategy successfully visualized the dynamic exchange of RSS between mitochondria and lysosomes.
• The study provides the first evidence of RSS involvement in inter-organelle communication at MLCs.
• The developed probe is non-toxic, sensitive, and capable of differentiating RSS localization.

Conclusions:

• The CDtSC strategy enables the visualization and analysis of rapid inter-organelle ion exchange events at nanometer resolution.
• This approach offers a new tool for studying cellular communication and organelle crosstalk.
• The findings highlight the role of RSS in inter-organelle communication at MLCs.