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Researchers from the University of Cologne discovered how a specific dietary amino acid increases cellular energy, opening new possibilities for treating metabolic diseases/publication in “Nature Cell Biology”
Mitochondria are the small organelles that generate the energy our bodies need to grow, move, and stay healthy. As mitochondria have to constantly adjust their function to meet the cell’s energy demands, the process of energy production is highly adaptable and is known to be adjusted by the nutrients available to the cell at a given moment. However, until now, it has been unclear how nutrients influence this adaptation. Now, a research team led by Professor Dr Thorsten Hoppe from the Institute for Genetics and the CECAD Cluster of Excellence on Aging Research at the University of Cologne identified a novel pathway through which the amino acid leucine enhances mitochondrial function. The new findings demonstrate how leucine stabilizes key mitochondrial proteins and boosts energy production. They have been published under the title “Leucine inhibits degradation of outer mitochondrial membrane proteins to adapt mitochondrial respiration” in Nature Cell Biology. Leucine is an essential amino acid, meaning it must be obtained through the diet. It is an important building block for protein synthesis and can be found in protein-rich foods such as dairy, meat, and legumes, such as beans and lentils. The researchers now found that leucine prevents the degradation of specific proteins present on the surface of mitochondria. These proteins support energy production by importing other metabolic molecules into the mitochondria. By preserving these proteins, leucine enables mitochondria to function more efficiently, ultimately boosting the cell’s energy production. “We were thrilled to discover that a cell’s nutrient status, especially its leucine levels, directly impacts energy production” said Dr Qiaochu Li, first author of the study. “This mechanism enables cells to swiftly adapt to increased energy demands during periods of nutrient abundance.” The team also discovered that this regulation is mediated by SEL1L, a protein involved in cellular quality control. SEL1L typically identifies damaged or misfolded proteins for degradation. Leucine appears to downregulate SEL1L, thus reducing the degradation of mitochondrial proteins and consequently enhancing mitochondrial performance. “Modulating leucine and SEL1L levels could be a strategy to boost energy production,” Li added. “However, it is important to proceed with caution. SEL1L also plays a crucial role in preventing the accumulation of damaged proteins, which is essential for long-term cellular health.” Indeed, while exploring the broader implications of their findings using the model organism Caenorhabditis elegans, the team observed that defects in leucine breakdown can negatively affect mitochondrial function and lead to fertility problems. Using human lung cancer cells, they also observed that certain cancer cell mutations that affect leucine metabolism enhance cancer cell survival, an important factor to consider in future cancer therapies. These new findings provide important new evidence that the nutrients in our diet not only fuel the body, but also actively shape how energy is produced at the cellular level. By revealing how leucine influences mitochondrial metabolism, this study identifies potential new therapeutic targets for diseases associated with impaired energy production, such as cancer and metabolic disorders. This research was supported by Germany’s Excellence Strategy in the framework of CECAD as well as by various Collaborative Research Centres funded by the German Research Foundation (DFG). Additional support was provided by the European Research Council through the ERC Advanced Grant “Cellular Strategies of Protein Quality Control-Degradation” (CellularPQCD), and the Alexander von Humboldt Foundation. Media Contact: Dr Thorsten Hoppe Institute for Genetics, University of Cologne +49 221 478 842 18 thorsten.hoppe[at]uni-koeln.de Press and Communications Team: Dr Anna Euteneuer +49 221 470 1700 a.euteneuer[at]verw.uni-koeln.de Publication: https://www.nature.com/articles/s41556-025-01799-3
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The German Research Foundation (DFG) is funding a new Research Unit focused on the regulation of the quality control of proteins that ensure the functioning of all our cells. 4.1 million euros over four years The German Research Foundation (DFG) will provide funding of 4.1 million euros over four years to a Research Unit from the life sciences at the University of Cologne focused on the regulation of proteostasis. Proteostasis plays an important role in the function and viability of cells: It ensures that proteins are produced and function properly, and that faulty proteins are degraded. Proteostasis is maintained by a network of quality control pathways. However, the capacity of this control system is limited. If it no longer works properly, cell function is impaired, which can lead to metabolic diseases, cancer and neurological disorders. The new Research Unit ‘Cell Non-Autonomous Regulation of Organismal Proteostasis’ (FOR 5762) focuses on deciphering the molecular mechanisms underlying the regulation of proteostasis – whether in a healthy or diseased state.
Professor Dr Joybrato Mukherjee, Rector of the University of Cologne, said: “I congratulate my colleagues on their success. The Research Unit will make valuable contributions to understanding the ageing process and the causes of age-related diseases. It is a great asset to the university’s Key Profile Area ‘Aging-Associated Diseases’.” The Research Unit’s work is based on the assumption that proteostasis is balanced by exchange mechanisms between different tissues. The aim is to understand how the quality control pathways function across organs and react to environmental and metabolic changes. The spokesperson is Professor Dr David Vilchez from the University of Cologne’s Faculty of Medicine and CECAD, the Cologne Cluster of Excellence for Aging Research. The deputy spokesperson is Professor Dr Thorsten Hoppe from the University of Cologne’s Faculty of Mathematics and Natural Sciences and CECAD. Both will coordinate this Research Unit. In addition to other researchers from the Faculty of Mathematics and Natural Sciences, researchers from the University of Konstanz are also involved. “As the proteostasis network is constantly challenged by changing metabolic, environmental and pathological conditions, maintaining a healthy proteome in all tissues is a lifelong task for the organism,” explains Professor Dr David Vilchez. “While the cell-autonomous mechanisms of quality control are well understood, only recently has there been evidence of systemic coordination of proteostasis between different tissues.” These findings indicate that there are non-autonomous communication pathways between cells that integrate and balance proteostasis mechanisms in different tissues to maintain the organism’s proteome. The researchers aim to understand the dynamic regulation of quality control pathways in organisms that integrate environmental and metabolic changes. The interdisciplinary project will combine biochemical, cell biological, (opto)genetic, proteomic and metabolomic approaches to define the molecular mechanisms underlying the regulation of proteostasis of organisms under different physiological and pathological conditions. With the new Research Unit, the University of Cologne now has a total of five Research Units for which its members act as spokespersons; four spokespersons conduct research at the Faculty of Medicine. It also participates in thirteen other DFG Research Units. Media Contact: Professor Dr David Vilchez CECAD – Cologne Cluster of Excellence for Aging Research +49 221 478 84172 dvilchezuni-koeln.de Press and Communications Team: Jan Voelkel +49 221 470 2356 j.voelkelverw.uni-koeln.de |
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