Biological complexity: neural controls over mitochondria (Introduction)

by David Turell , Wednesday, February 03, 2021, 18:26 (1389 days ago) @ David Turell

The transfer of a key enzyme is under neural controls:

https://phys.org/news/2021-02-neural-mitochondrial-rna-nucleus.html

"...researchers show that mitochondria translocate their key RNA methyltransferase enzyme, TRMT1, into host cell nuclei in response to neural activity. This subcellular relocalization of key RNA modifiers suggests a new understanding of how neurons plastically reconfigure their nuclei as network dynamics change.

"While epigenetic processes involving DNA methylation and histone modifications are known to be critical in learning and memory, the role of RNA modifications in cognitive function has been less well characterized.

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"The researchers found that depolarization of neurons using KCL caused the relocation of TRMT1 from mitochondria and cytosol, as well as the relocation of TRMT1L from the nucleolus, into small punctate compartments of the nucleus. Although short depolarization bursts with KCL has been used to mimic long-term potentiation (LTP) via induction of immediate early genes, it is not a perfect simulator of real neural activity. In order to do that, fast electrical stimulation should be used to generate individual spike trains from individual neurons.

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"An important question in all this is how mitochondria know that the neuron is firing, and furthermore, how they send TRMT1 to the nucleus. While it is known that mitochondria can rapidly respond to the influx of calcium that occurs during depolarization of tiny pre- or postsynaptic structures, these signals would likely wash out, temporally, near the nucleus inside of a large neuron.

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"As far as the second question, the transfer of molecules from mitochondria to nucleus is a nice trick that cells regularly employ to control genes and epigenetic structure. For example, ATFS-1 (activating transcription factor associated with stress), which mediates the mitochondrial uncoupling response, is often translocated into the nucleus to modify gene expression. Similarly, PDC (pyruvate decarboxylase) can enter the nucleus under certain conditions to generate acetyl-CoA for histone acetylation.

"For the case of TRMT1, the presence of a strong MLS peptide overrides the weak NLS and the protein is initially targeted to mitochondrial transporters upon being synthesized. After entry, various proteases immediately cleave the signal sequence and activate the protein. Later on, contingent upon sufficient depolarization or other presumptive mitoflash events, the protein can exit the mitochondria. This time, lacking the MLS, the weak NLS eventually brings the protein back home to the nucleus."

Comment: a highly technical article with many processes and molecules described. It is another example of the intense complexity that dictates neuron activity with their mitochondria, and demands that one accept design as the source.