Mitochondria adjust their energy output based on nutrient availability, but how individual nutrients send signals has been unclear. Researchers at the University of Cologne have now identified a new mechanism: the essential amino acid leucine can stabilize proteins on the outer mitochondrial membrane, allowing the organelles to produce energy more efficiently. The study, published in Nature Cell Biology, was led by Professor Thorsten Hoppe and first author Qiaochu Li.
The team traced the effect to SEL1L, a protein involved in cellular quality control. SEL1L normally helps mark damaged or unneeded proteins for degradation. Leucine appears to reduce SEL1L activity, so fewer mitochondrial proteins are broken down and more remain available to support respiration. As Li explained, this lets cells quickly adapt to increased energy demands when nutrients are abundant.
The researchers also studied C. elegans worms and human lung cancer cells. In worms, disrupted leucine breakdown led to mitochondrial problems and fertility issues; in cancer cells, certain mutations in leucine metabolism helped the cells survive. The authors caution that SEL1L also removes defective proteins, so boosting energy production by modulating this pathway could have unintended consequences. The findings add to evidence that nutrients act as signals, not just fuel, and point to potential targets for metabolic disorders and cancer.