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Updated: May 8, 2026
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Analysis of the Mitochondrial Density and Longitudinal Distribution in Rat Live-Skeletal Muscle Fibers by Confocal Microscopy
Published on: December 1, 2023
Mitochondrial dysfunction and calcium deregulation by the RanBP9-cofilin pathway
Seung-Eon Roh1, Jung A Woo, Madepalli K Lakshmana
11Department of Molecular Medicine, USF Health Byrd Institute, 4001 E. Fletcher Ave., Tampa, FL 33613, USA. dkang@health.usf.edu.
Summary
The scaffolding protein RanBP9 worsens Alzheimer's disease (AD) by increasing amyloid beta (Aβ) and impairing mitochondrial function. RanBP9 disrupts calcium handling and axonal transport, leading to neurodegeneration.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Alzheimer's disease (AD) involves mitochondrial dysfunction and synaptic damage, linked to amyloid beta (Aβ) and tau pathology.
- The scaffolding protein RanBP9 is elevated in AD brains and promotes Aβ generation and neurodegeneration.
Purpose of the Study:
- To investigate the role of RanBP9 in Aβ-induced mitochondrial dysfunction and neurotoxicity in primary hippocampal neurons.
- To elucidate the mechanisms by which RanBP9 affects calcium homeostasis and mitochondrial transport.
Main Methods:
- Primary hippocampal neuron cultures were used to assess Aβ-induced reactive oxygen species (ROS) production, apoptosis, and calcium deregulation.
- Calcium-handling measures, including mitochondrial calcium uniporter activity and cytosolic Ca(2+) clearance, were analyzed.
- Mitochondrial transport and synaptic mitochondrial activity were evaluated in neurons and brain tissue.
Main Results:
- RanBP9 potentiates Aβ-induced ROS overproduction, apoptosis, and calcium deregulation.
- RanBP9 delays cytosolic Ca(2+) clearance via mitochondrial mechanisms involving cofilin translocation and oxidative stress.
- RanBP9 impairs anterograde axonal transport of mitochondria and reduces synaptic mitochondrial activity.
Conclusions:
- RanBP9, cofilin, and Aβ interact to exacerbate mitochondrial dysfunction, ROS production, and calcium deregulation.
- These combined effects contribute to neurodegenerative changes characteristic of Alzheimer's disease.
- RanBP9 represents a potential therapeutic target for mitigating AD-related neurodegeneration.
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