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Updated: Feb 17, 2026

Understanding the Changes in Mitochondrial Morphology through Dynamic and Three-dimensional Fluorescence Micrographs
Published on: August 15, 2025
Ionic signalling and mitochondrial dynamics
Nada Abuarab1, Fangfang Li1, Asipu Sivaprasadarao1,2
1School of Biomedical Sciences, Faculty of Biological Sciences, LS2 9JT, Leeds, U.K.
Abstract:
In age-related diseases, rise in intracellular reactive oxygen species (ROS) causes fragmentation of mitochondrial network. Our recent study demonstrated that ROS activation of TRPM2 (transient receptor potential melastatin-2) channels triggers lysosomal Zn2+ release that, in turn, triggers mitochondrial fragmentation. The findings provide new mechanistic insights that may have therapeutic implications.
Insights
Increased reactive oxygen species (ROS) fragment mitochondria in aging. Our study shows ROS-activated TRPM2 channels release lysosomal zinc, causing mitochondrial fragmentation, offering therapeutic insights.
Area of Science:
- Cellular Biology
- Mitochondrial Dynamics
- Age-Related Diseases
Background:
- Elevated intracellular reactive oxygen species (ROS) are implicated in age-related diseases.
- Mitochondrial fragmentation is a hallmark of cellular aging and disease.
- The precise mechanisms linking ROS to mitochondrial fragmentation require further elucidation.
Purpose of the Study:
- To investigate the role of TRPM2 channels in ROS-induced mitochondrial fragmentation.
- To elucidate the downstream signaling pathway involving lysosomal zinc release.
- To explore potential therapeutic targets for age-related mitochondrial dysfunction.
Main Methods:
- Utilized cellular models to study reactive oxygen species (ROS) signaling.
- Investigated the function of TRPM2 channels using specific inhibitors and genetic approaches.
- Assessed lysosomal zinc release and mitochondrial morphology via advanced microscopy techniques.
Main Results:
- Demonstrated that ROS directly activate TRPM2 channels.
- Showcased TRPM2 channel activation leading to lysosomal Zn2+ release.
- Confirmed that lysosomal zinc triggers mitochondrial fragmentation.
Conclusions:
- ROS-activated TRPM2 channels represent a critical link to mitochondrial fragmentation.
- Lysosomal zinc release is a key mediator in this process.
- Targeting the TRPM2-lysosomal-mitochondrial axis may offer therapeutic strategies for aging.
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