Related Experiment Video
Updated: Jun 3, 2026
08:15
Understanding the Changes in Mitochondrial Morphology through Dynamic and Three-dimensional Fluorescence Micrographs
Published on: August 15, 2025
Combining Fret and Super-Resolution Microscopy Reveals Kinase Activation and Mitochondrial Activity at the Nanoscale
Nicolas Y Jolivet1, Pierre-Jean Desmaison1, Xavier Pinson2
1CNRS, Univ Rennes, IGDR [(Institut De Génétique Et Développement De Rennes)] - UMR 6290, Rennes, France.
Summary
Researchers developed BioSenSRRF, a new microscopy method, to visualize Aurora kinase A (AURKA) activity in mitochondria with high spatial resolution. This technique reveals compartmentalized kinase activity linked to ATP synthase, offering insights into mitochondrial function and cancer-associated mutations.
Area of Science:
- Cell Biology
- Molecular Biology
- Microscopy
Background:
- Protein kinases regulate intracellular signaling within specific subcellular compartments.
- Genetically encoded Förster's resonance energy transfer (FRET) biosensors track kinase dynamics but often lack spatial resolution.
- Aurora kinase A (AURKA) is a key regulator of mitochondrial physiology, but its precise activation and activity visualization remain challenging.
Purpose of the Study:
- To introduce BioSenSRRF, a novel approach combining FRET biosensors with super-resolution radial fluctuations (SRRF) microscopy.
- To enhance the spatial resolution of genetically encoded biosensors for studying kinase dynamics.
- To investigate the subcellular localization and compartmentalization of AURKA activity within mitochondria.
Main Methods:
- Developed and implemented the BioSenSRRF approach, integrating FRET biosensors with SRRF microscopy.
- Utilized standard microscopy setups and publicly available image analysis tools.
- Applied the method to visualize mitochondrial AURKA activation and activity in distinct domains.
Main Results:
- Discovered that mitochondrial AURKA activation and activity are compartmentalized into specific domains associated with ATP synthase.
- Demonstrated that these subdomains are dependent on AURKA catalytic activity and can be modulated by AURKA inhibitors.
- Showed that the cancer-associated polymorphism F31I enhances AURKA activation and ATP production within these subdomains.
Conclusions:
- BioSenSRRF provides a broadly accessible framework to improve the spatial resolution of genetically encoded biosensors.
- Revealed compartmentalization of mitochondrial AURKA activity within ATP synthase-enriched subdomains.
- Opened new avenues for dissecting kinase subcellular organization in physiology and disease, including the role of cancer-associated polymorphisms.
