Neurons Optimize Energy for Synaptic Efficiency

Neurons must balance energy efficiency with the need to produce and transport proteins essential for their function. A study by researchers from the University Hospital Bonn, the University of Bonn, and the University Medical Center Göttingen shows that neurons regulate messenger RNA (mRNA) and protein distribution based on molecular properties such as size and stability. The findings, published in Nature Communications, suggest that this energy-saving strategy helps neurons maintain synaptic function while minimizing resource waste.

Energy constraints shape protein localization

Despite its small size, the brain requires approximately 20% of the body's total energy. Neurons operate within strict metabolic limits, particularly concerning the synthesis, transport and degradation of molecules. To minimize unnecessary energy expenditure, neurons produce proteins in locations where they will be used rather than transporting them across long distances.

Proteins are synthesized from mRNA, which carries genetic instructions from DNA. Advances in microscopy and biochemistry now allow researchers to map the precise locations of mRNA and proteins within neurons, revealing complex organizational patterns that optimize cellular efficiency. By analyzing large-scale mRNA and proteomic datasets, the researchers found that neuronal energy conservation strategies vary based on the properties of each molecular species.

Dendritic synthesis reduces energy loss

The study highlights that energy-efficient protein synthesis depends on molecular longevity and transport dynamics. Short-lived proteins produced in the neuronal cell body may degrade before reaching distant synapses, leading to wasted resources. As a solution, neurons preferentially synthesize these proteins in dendrites – the branched extensions of the cell – if the energy cost of mRNA transport is lower than that of protein transport. This localized protein production strategy reduces overall energy expenditure while maintaining necessary synaptic functions.

"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."

Prof. Tatjana Tchumatchenko.

Broader implications for gene expression

Beyond energy efficiency, the findings provide new insights into the broader principles governing gene expression. The study suggests that physical properties of molecules, such as their lifespan and length, play a more significant role in determining their spatial distribution than previously recognized. These principles apply across different molecular species and may help researchers reinterpret existing gene expression datasets.

The ability to predict where specific proteins are synthesized in neurons based on their properties could contribute to future research on neurodegenerative diseases and synaptic plasticity. By understanding how neurons optimize protein distribution, scientists may uncover new targets for therapeutic interventions that address disruptions in cellular energy management.

Reference: Bergmann C, Mousaei K, Rizzoli SO, Tchumatchenko T. How energy determines spatial localisation and copy number of molecules in neurons. Nat Commun. 2025;16(1):1424. doi: 10.1038/s41467-025-56640-0

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