Nerve cells utilize remarkable tactics to conserve energy while still fulfilling their crucial roles. Research teams from the University Hospital Bonn (UKB), the University of Bonn, and the University Medical Center Göttingen discovered that the energy-saving mechanisms in neurons dictate where messenger RNA (mRNA) and proteins are situated and how many there are, varying according to the characteristics like length and lifespan of these molecules. Their findings are now available in the journal Nature Communications.
We’ve all felt the need to conserve energy in recent times, leading us to devise methods that help us meet our essential needs. Similarly, nerve cells face a challenge: they must supply their synapses, the points where they connect with other neurons, while arranging their protein production efficiently to avoid over or underproduction. Additionally, they have to transport proteins over substantial distances to the synapses while keeping an eye on their energy budget. “How do they achieve this?” queried the research group led by Prof. Tatjana Tchumatchenko, head of the Institute for Experimental Epileptology and Cognition Research at the UKB and member of the Transdisciplinary Research Areas (TRA) “Life and Health” and “Modeling” at the University of Bonn.
Ways to Save Energy Clarify Protein Distribution
Even though the brain is relatively small, it uses about 20 percent of the body’s total energy. Neuronal activities are bound by strict energy limitations, which are notably severe in the high-energy-demand environment of the brain. The research team revealed that the synthesis and breakdown of neuronal molecules involve significant energy consumption, necessitating energy-saving strategies. Like all cells, neurons depend on proteins, which are formed via a process called gene expression, where information is copied from a gene into messenger RNA (mRNA). This mature mRNA is then translated into the necessary protein. Thanks to advancements in biochemistry and microscopy, researchers can now accurately locate and quantify individual mRNA copies and corresponding proteins in cells, analyzing thousands of mRNA and protein types. This marks the first time scientists can explore intricate organizational principles governing spatial gene expression patterns across various molecules.
The research group amalgamated experimental data from over ten extensive mRNA and proteomics analyses involving tens of thousands of molecular species. “Our findings indicate that the quest for energy conservation influences mRNA and protein numbers and their distributions, with each molecular species responding differently based on factors like length, lifespan, and other characteristics,” shares first author Cornelius Bergmann, a PhD candidate from the University Bonn at the Institute of Experimental Epileptology and Cognition Research at the UKB.
The findings reveal that the energy costs linked to the synthesis, transport, and degradation of molecules, alongside their spatial arrangement and overall quantity, limit solutions to energy-efficient options. “If some transient proteins were produced in the cell body, a significant portion would not survive the lengthy journey to the synapses,” Prof. Tchumatchenko explains. “This would lead to energy wastage on proteins that can’t perform their function.” The study’s models indicate that proteins are preferentially synthesized in the branching extensions of a nerve cell, known as dendrites, when the energy loss during the journey from the cell body to the synapses exceeds the energy needed to move the mRNA into the dendrites.
A Fresh Perspective on Gene Expression Research
The insights from the research team extend beyond just energy conservation. “Our findings illuminate the organizational principles of gene expression within cells, highlighting interactions across various molecular types and going beyond isolated regulatory systems,” states co-author Prof. Silvio Rizzoli, head of the Department of Neuro- and Sensory Physiology at the University Medical Center Göttingen, spokesperson for the Center for Biostructural Imaging of Neurodegeneration (BIN), and a member of the Cluster of Excellence “Multiscale Bioimaging: from molecular machines to networks of excitable cells” (MBExC).
One of the most unexpected discoveries for the team was that the physical characteristics of proteins—such as their length and lifespan—rather than their specific functions, significantly impact energy efficiency and consequently influence where they are synthesized. Co-author Kanaan Mousaei, a doctoral candidate at the University Bonn from the Institute of Experimental Epileptology and Cognition Research at the UKB, remarks: “Our model provides a new perspective for linking together numerous existing data sets from various laboratories.”
