Related Experiment Video
Updated: Nov 20, 2025
07:40
Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy
Published on: May 26, 2023
1.4K
BNIP3L/NIX-mediated mitophagy protects against glucocorticoid-induced synapse defects
Gee Euhn Choi1, Hyun Jik Lee2,3, Chang Woo Chae1
1Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, and BK21 Four Future Veterinary Medicine Leading Education & Research Center, Seoul National University, Seoul, 08826, South Korea.
Nature Communications
|January 21, 2021
Summary
Glucocorticoids impair synaptic function by inhibiting mitophagy, a cellular cleanup process. Activating NIX, a key mitophagy regulator, can restore synaptic density and improve memory in mice.
Area of Science:
- Neuroscience
- Cell Biology
- Mitochondrial Biology
Background:
- Stress hormones like glucocorticoids disrupt mitochondrial function.
- Damaged mitochondria accumulate instead of being cleared by mitophagy.
- This accumulation is linked to synaptic dysfunction.
Purpose of the Study:
- To investigate how glucocorticoids inhibit mitophagy.
- To understand the role of mitophagy inhibition in synaptic defects.
- To identify molecular targets for restoring synapse function.
Main Methods:
- Studied hippocampal neurons, SH-SY5Y cells, and ICR mice.
- Assessed synaptic density and vesicle recycling.
- Analyzed mitochondrial respiration and mitophagy markers.
- Investigated glucocorticoid receptor binding to the PGC1α promoter.
- Used NIX enhancer pre-treatment in a mouse model.
Main Results:
- Glucocorticoids decrease synaptic density and vesicle recycling by suppressing mitophagy.
- Glucocorticoids downregulate BNIP3-like (BNIP3L)/NIX, impairing mitochondrial respiration and synaptic density.
- Glucocorticoid receptor activation downregulates PGC1α, selectively decreasing NIX-dependent mitophagy.
- NIX enhancer pre-treatment in mice improved mitophagy, synaptic density, and spatial memory.
Conclusions:
- Glucocorticoids inhibit mitophagy by downregulating NIX.
- NIX activation is a potential therapeutic target for restoring synapse function and cognitive deficits.
