Light-activated mitochondrial fission through optogenetic control of mitochondria-lysosome contacts
Kangqiang Qiu1, Weiwei Zou2, Hongbao Fang1
1Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
Abstract:
Mitochondria are highly dynamic organelles whose fragmentation by fission is critical to their functional integrity and cellular homeostasis. Here, we develop a method via optogenetic control of mitochondria-lysosome contacts (MLCs) to induce mitochondrial fission with spatiotemporal accuracy. MLCs can be achieved by blue-light-induced association of mitochondria and lysosomes through various photoactivatable dimerizers. Real-time optogenetic induction of mitochondrial fission is tracked in living cells to measure the fission rate. The optogenetic method partially restores the mitochondrial functions of SLC25A46-/- cells, which display defects in mitochondrial fission and hyperfused mitochondria. The optogenetic MLCs system thus provides a platform for studying mitochondrial fission and treating mitochondrial diseases.
Insights
Researchers developed optogenetic control of mitochondria-lysosome contacts to induce mitochondrial fission. This method aids in studying mitochondrial dynamics and offers potential for treating mitochondrial diseases.
Area of Science:
- Cell Biology
- Mitochondrial Biology
- Optogenetics
Background:
- Mitochondria are dynamic organelles essential for cellular homeostasis.
- Mitochondrial fission, the fragmentation of mitochondria, is crucial for maintaining mitochondrial function and cellular health.
- Defects in mitochondrial fission are linked to various mitochondrial diseases.
Purpose of the Study:
- To develop a spatiotemporally accurate method for inducing mitochondrial fission.
- To investigate the role of mitochondria-lysosome contacts (MLCs) in regulating mitochondrial fission.
- To explore the therapeutic potential of optogenetically controlled mitochondrial fission for mitochondrial diseases.
Main Methods:
- Utilized optogenetics to control mitochondria-lysosome contacts (MLCs) via blue-light-induced photoactivatable dimerizers.
- Developed a system for real-time optogenetic induction and tracking of mitochondrial fission in living cells.
- Assessed mitochondrial function in SLC25A46-/- cells with induced mitochondrial fission.
Main Results:
- Successfully induced mitochondrial fission with spatiotemporal precision using optogenetic control of MLCs.
- Established a method to measure mitochondrial fission rates in real-time.
- Demonstrated partial restoration of mitochondrial function in SLC25A46-/- cells with defective fission.
Conclusions:
- Optogenetic control of MLCs provides a powerful tool for studying mitochondrial fission.
- This system offers a potential platform for developing new therapeutic strategies for mitochondrial diseases characterized by fission defects.
More Related Videos
11:00Photostimulation by Femtosecond Laser Activates Extracellular-signal-regulated Kinase ERK Signaling or Mitochondrial Events in Target Cells
Published on: July 6, 2019
09:29Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy
Published on: May 4, 2016
