The newly-discovered neuronal back-up system safeguards metabolic flexibility of neurons to cope with energy demands of electrical signaling, according to a team of researchers from the Center of Physiology and Pharmacology at the Medical University of Vienna.
Dhoundiyal et al. discovered that neurons have an emergency back-up system to enable them to remain functional even when their energy supply is disrupted. Image credit: Colin Behrens.
In their study, Medical University of Vienna neuroscientists Matej Hotka and Helmut Kubista and their colleagues established that each neuron has three regulatory systems.
If one of these systems fails, another one takes over and ensures that sufficient energy is supplied to meet the prevailing requirement.
Specifically, the researchers identified the glycerol-3-phosphate shuttle system (G3PS) as an essential back-up.
Until now, the existence of this biochemical transport mechanism in neurons has been questioned, because a different system — malate-aspartate shuttle (MAS) — predominates there. However, the G3PS is vitally important in neurons.
The authors also found that the deployment of the neuronal emergency back-up system follows a hierarchy: while the first two regulatory mechanisms share their back-up duties, the third only comes into play if the other two fail to function adequately.
“One reason for this is very likely that deployment of system number three goes hand-in-hand with an adverse side-effect,” Dr. Kubista said.
“It leads to the formation of oxygen radicals, which can cause damage to nerve cells if they are present in large quantities.”
“That’s probably why this system only steps in when energy demand can’t be met via the other two systems.”
The interplay between the three regulatory systems serves to prevent any under- or oversupply or the possibility of complete energy failure.
“The role of G3PS in acute defense against neuronal emergencies may contribute to research of various brain dysfunctions, such as those caused by congenital defects in the MAS regulatory mechanism,” the scientists said.
“For example, new insights and therapeutic approaches for a form of early childhood epileptic encephalopathy could follow if G3PS can also be detected in neurons of the human brain.”
The findings were published this week in the Journal of Neuroscience.
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Ankit Dhoundiyal et al. Glycerol-3-phosphate shuttle is a backup system securing metabolic flexibility in neurons. Journal of Neuroscience, published online August 23, 2022; doi: 10.1523/JNEUROSCI.0193-22.2022
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