Mitochondria are often described as the powerhouses of the cell because they produce much of the energy our bodies need to grow, move, repair tissues, and perform daily functions. But they don’t operate at a constant pace. Instead, mitochondria continually adjust their activity based on the amount of energy a cell needs and the nutrients available.
Scientists have long known that nutrition can influence this process. What is less clear is exactly how individual nutrients send signals that change mitochondrial activity.
Now, researchers led by Professor Thorsten Hoppe from the Institute of Genetics and the CECAD Excellence Group on Aging Research at the University of Cologne have identified a new mechanism involving the amino acid leucine. Their results show that leucine can help stabilize important proteins in mitochondria, allowing the organelles to produce energy more efficiently.
The study, published in Natural cellular biologyis titled “Leucine inhibits the breakdown of outer mitochondrial membrane proteins to adapt mitochondrial respiration.”
How Leucine Helps Mitochondria Produce Energy
Leucine is an essential amino acid, which means the human body cannot make enough of it on its own and must obtain it through diet. Amino acids are the building blocks used to make proteins, and leucine is particularly abundant in protein-rich foods such as dairy, meat, beans and lentils.
Researchers have found that leucine does more than contribute to protein production. It also helps prevent the breakdown of certain proteins located on the outer surface of mitochondria.
These proteins play an important role in metabolism because they help move other molecules to the mitochondria, where they can be used as part of the cell’s energy-producing machinery. When leucine helps preserve these proteins, the mitochondria can function more efficiently and increase the amount of energy produced by the cell.
“We were excited to discover that a cell’s nutritional status, particularly its leucine levels, has a direct impact on energy production,” said Dr. Qiaochu Li, first author of the study. “This mechanism allows cells to quickly adapt to increased energy demands during periods of nutrient abundance.”
A cellular quality control protein plays a key role
The team attributed this effect to a protein called SEL1L, involved in cell quality control.
Cells constantly inspect their proteins, because damaged or misfolded proteins can interfere with their normal function. SEL1L helps identify proteins that need to be removed and directs them toward degradation.
According to the researchers, leucine appears to reduce SEL1L activity. This means that fewer mitochondrial proteins are broken down, allowing more of them to stay in place and support mitochondrial function.
“Modulating leucine and SEL1L levels could be a strategy to stimulate 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.”
This warning is important because increasing energy production is not automatically beneficial in all situations. The same cellular systems that preserve useful proteins also help eliminate defective proteins, so changing this balance could have unintended consequences.
Effects on fertility and cancer cells
To explore the broader effects of leucine metabolism, researchers also studied Caenorhabditis elegansa small roundworm commonly used in biology because many of its cellular processes are similar to those found in more complex organisms.
In worms, problems with leucine breakdown disrupted mitochondrial function and were linked to fertility problems.
The scientists also looked at human lung cancer cells. They discovered that certain mutations affecting leucine metabolism could help cancer cells survive. This observation could be important for future cancer research because treatments that alter leucine-related pathways may affect healthy cells and tumor cells in different ways.
Diet does more than provide fuel
These findings add to growing evidence that nutrients do more than just provide raw materials for the body. They can also act as signals that influence how cells function.
In this case, leucine appears to help cells adjust energy production based on nutrient availability by protecting key mitochondrial proteins from degradation.
By revealing this previously unknown link between leucine, protein quality control and mitochondrial metabolism, researchers have identified new potential targets for diseases in which cellular energy production is disrupted, including cancer and metabolic disorders.
The work was supported by the German Excellence Strategy under CECAD as well as various collaborative research centers funded by the German Research Foundation (DFG). Additional support was provided by the European Research Council through the ERC Advanced Grant “Cellular Strategies for Protein Quality Control-Degradation” (CellularPQCD) and the Alexander von Humboldt Foundation.
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