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 carry out everyday functions. But they do not operate at a constant pace. Instead, mitochondria continuously adjust their activity depending on how much energy a cell needs and which nutrients are available.
Scientists have long known that nutrition can influence this process. What has been less clear is exactly how individual nutrients send signals that change mitochondrial activity.
Now, researchers led by Professor Dr. Thorsten Hoppe of the Institute for Genetics and the CECAD Cluster of Excellence on Aging Research at the University of Cologne have identified a new mechanism involving the amino acid leucine. Their findings show that leucine can help stabilize important proteins in mitochondria, allowing the organelles to produce energy more efficiently.
The study, published in Nature Cell Biology, is titled “Leucine inhibits degradation 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 food. Amino acids are the building blocks used to make proteins, and leucine is especially abundant in protein rich foods such as dairy products, meat, beans, and lentils.
The researchers 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.
Those proteins play an important role in metabolism because they help move other molecules into mitochondria, where they can be used as part of the cell’s energy producing machinery. When leucine helps preserve these proteins, mitochondria can operate more effectively and increase the amount of energy the cell produces.
“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.”
A Cellular Quality Control Protein Plays a Key Role
The team traced this effect to a protein called SEL1L, which is involved in cellular quality control.
Cells constantly inspect their proteins because damaged or incorrectly folded proteins can interfere with normal function. SEL1L helps identify proteins that should be removed and directs them toward degradation.
According to the researchers, leucine appears to reduce the activity of SEL1L. That means fewer mitochondrial proteins are broken down, allowing more of them to remain in place and support mitochondrial function.
“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.”
That warning is important because increasing energy production is not automatically beneficial in every situation. The same cellular systems that preserve useful proteins also help eliminate defective ones, so changing that balance could have unintended consequences.
Effects on Fertility and Cancer Cells
To explore the broader effects of leucine metabolism, the researchers also studied Caenorhabditis elegans, a tiny roundworm commonly used in biology because many of its cellular processes are similar to those found in more complex organisms.
In the worms, problems with leucine breakdown disrupted mitochondrial function and were linked to fertility problems.
The scientists also examined human lung cancer cells. They found that some mutations affecting leucine metabolism could help cancer cells survive. That observation could be important for future cancer research because treatments that alter leucine related pathways may affect both healthy cells and tumor cells in different ways.
Diet Does More Than Supply Fuel
The findings add to growing evidence that nutrients do more than simply provide raw material 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 according to nutrient availability by protecting key mitochondrial proteins from degradation.
By revealing this previously unknown link between leucine, protein quality control, and mitochondrial metabolism, the researchers have identified potential new targets for diseases in which cellular energy production is disrupted, including cancer and metabolic disorders.
The work 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.
