Introducing the brain: mitochondria stationary in neurons (Introduction)

by David Turell , Wednesday, March 13, 2024, 20:02 (253 days ago) @ David Turell

All along the axons and dendrites:

https://www.the-scientist.com/how-mitochondria-stay-still-in-neurons-71720?utm_campaign...

"In a recent study, Rangaraju and her team described how the vesicle-associated membrane protein-associated protein (VAP) stabilizes mitochondria in dendrites, the branch-like structures neurons use to receive information from other neurons. They also showed that knocking out the VAP gene impaired the plasticity of dendritic spines. These findings, published in Nature Communications, suggest a role for VAP in mitochondria spatial stability and synaptic plasticity in dendrites.

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"Mitochondria are the main suppliers of energy to neurons, but they look and behave differently depending on where they are situated in the brain cell. Mitochondria located in the axon, a neuron’s output structure, are discrete organelles that are either stationary or motile.2 In contrast, mitochondria are jammed together and often overlap in dendrites.

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"Rangaraju and her colleagues found that, in dendrites, the organelles form long structures called mitochondrial compartments that often consist of stacked mitochondrial filaments.3 The team also showed that these compartments tether to the cytoskeleton and stay in the same place for up to two hours, providing energy for local protein synthesis and synaptic plasticity.

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"Mitochondria lacking the candidate protein VAP showed a reduction in length after photoactivation, suggesting destabilization of the dendritic mitochondrial compartment.

"The team next explored the functional relevance of these findings by assessing how VAP affected synaptic plasticity, the ability of synapses to strengthen or weaken over time. They measured changes in dendritic spine head size after stimulating the neurons since increases in the head size of these tiny protrusions often correlate with synaptic plasticity and brain processes, such as memory formation. The absence of VAP reduced the expected increase in spine head size after neuronal stimulation. Moreover, the dendritic spines of neurons lacking VAP did not maintain their sizes, but shrank over time.

“'It's really interesting that VAP was important for sustaining the anatomical change,” noted Schwarz.

"While Wang found the results compelling and convincing, she believes that an important next step is to evaluate whether the same mechanism can be detected in an in vivo setting. Additionally, because VAP is implicated in neurological diseases such as amyotrophic lateral sclerosis (ALS), she is curious to see if the same mechanism might be important in a disease context. Rangaraju plans to examine the role of VAP in ALS-related motor learning deficits in animal models and to obtain samples from patients with ALS to see if defects in mitochondrial stabilization and synaptic plasticity appear in patient-derived neurons."

Comment: stabilization of mitochondria is of extreme importance in neurons considering the length of many axons. Mitochondria supply localized energy.