New Study Reveals Energy-Saving Strategies in Neuronal Protein Synthesis

Nerve cells use incredible energy-saving techniques while still carrying out their primary functions. Researchers from the University of Bonn, the University Hospital Bonn (UKB), and the University Medical Center Göttingen discovered that the neuronal energy conservation program varies based on the length, longevity, and other characteristics of the corresponding molecule and determines the number and location of messenger RNA (mRNA) and proteins. The study was recently published in the Nature Communications journal.

In recent years, everyone has felt the urge to conserve energy. To do this, techniques must be devised for conserving energy while meeting the most basic demands.

Our nerve cells are facing a similar dilemma: They have to supply their synapses, i.e. their contact points with other neurons, but also organize their protein synthesis in such a way that they do not produce too much or too little proteins. At the same time, they have to transport the proteins over long distances to the synapses and also pay attention to their energy budget. How do they manage this?”

Dr. Tatjana Tchumatchenko, Study Corresponding Author and Professor, University of Bonn

Tchumatchenko is also the Research Group Leader at the Institute for Experimental Epileptology and Cognition Research at the UKB and a member of the Transdisciplinary Research Areas (TRA) “Life and Health” and “Modelling” at the University of Bonn.

Energy-Saving Measures Explain Protein Distributions

Despite its modest size, the brain requires approximately 20% of the body's total energy. Neuronal functions, like all cells, are subject to tight energy restrictions, which are particularly obvious in the brain due to its high energy demands.

The research team demonstrated that the synthesis and breakdown of all neuronal substances consume a significant amount of cellular energy, necessitating energy-saving strategies. All cells, including neurons, require proteins to operate properly.

These are produced through a process called gene expression, which involves copying important information from a gene into messenger RNA (mRNA). The mature mRNA is subsequently translated into the appropriate protein.

Advances in biochemistry and microscopy now allow us to precisely map the position of individual mRNA copies and matching proteins in cells, as well as estimate the quantity of thousands of mRNA and protein species. For the first time, researchers can explore complicated organizational principles that govern spatial gene expression patterns and apply them to all sorts of molecules.

The researchers pooled experimental data from over 10 large-scale mRNA and proteome screens that included tens of thousands of molecular species.

We found that the drive to conserve energy determines mRNA and protein number and location, affecting each molecular species differently depending on the length, lifetime, and other properties of the molecule.”

Cornelius Bergmann, Study First Author and PhD Student and, University of Bonn

The findings reveal that energy-efficient solutions are limited in terms of the energetic costs of molecule synthesis, transport, and degradation, as well as their spatial localization and overall quantity.

Dr. Tchumatchenko added, “If certain short-lived proteins were synthesized in the cell body, a large proportion of them would not arrive alive at the synapses due to the long travel time. This would be a waste of energy on proteins that cannot fulfill their task.”

According to the model calculations used in this study, if the energy loss "on the way" from the cell body to the synapses is greater than the energy needed to transport the mRNA into the dendrites, then proteins are preferentially synthesized in the branched, tapering extensions of a nerve cell, known as dendrites.

New Perspective on Gene Expression Studies

The research team's conclusions, however, go beyond energy conservation.

“Our results shed light on the organizational principles of gene expression in cells that act across different molecular species and go beyond individual regulatory mechanisms. Multiscale Bioimaging: from molecular machines to networks of excitable cells,” added Co-Author Professor Silvio Rizzoli, Director of the Department of Neuro- and Sensory Physiology at the University Medical Center Göttingen, spokesperson of the Center for Biostructural Imaging of Neurodegeneration (BIN), and member of the Cluster of Excellence “Multiscale Bioimaging: from molecular machines to networks of excitable cells” (MBExC).

The most striking finding for the research team was that the physical qualities of proteins, such as length or longevity, rather than their specialized function, have such a big influence on the energy budget and consequently the site of synthesis.

Co-author Kanaan Mousaei, a doctoral student at the University of Bonn’s Institute of Experimental Epileptology and Cognition Research at the UKB, emphasized, “Our model offers a new perspective for correlating dozens of existing data sets from different laboratories.”