The amino acid leucine may act as a nutrient signal that enhances mitochondrial function and increases cellular energy capacity. Digest
Mitochondria are often called the "powerhouses" of cells, and their proper function is essential for sustaining energy balance and health. In a new study, researchers at the University of Cologne investigated whether the amino acid leucine can directly influence their activity.
Using the roundworm C. elegans and cultured human cells, the scientists tested whether adding leucine could stabilize proteins on the outer mitochondrial membrane—the boundary that interacts with the rest of the cell—and how this affects mitochondrial metabolism. In some experiments, leucine was compared with the related branched-chain amino acids (BCAAs) isoleucine and valine, or with a broader panel of essential amino acids.
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Leucine produced rapid, specific changes in mitochondrial function:
- Within three hours, leucine increased maximal oxygen consumption in worms, indicating enhanced energy production; in human cells, both basal and maximal oxygen consumption rose, whereas other essential amino acids caused only slight respiration increases.
- In human cells and worms, leucine reduced the tagging of outer-mitochondrial-membrane proteins for degradation, without changing overall protein tagging elsewhere. In worms, the related BCAAs were also tested and did not have this effect on protein degradation.
- The effect depended on GCN2, a nutrient-sensing enzyme, and likely worked by lowering the amount of mitochondrial-associated SEL-1 in worms and SEL1L in human cells, quality-control proteins that normally team up with another enzyme to tag outer-mitochondrial proteins for removal.
- Leucine increased levels of several mitochondrial proteins such as TOMM40, which are part of the machinery that imports proteins into mitochondria and link energy production to the cell's overall metabolism.
- Blocking mitochondrial protein import prevented leucine from boosting energy production, indicating that the increase in protein import is essential for the effect.
Together, the findings describe a new pathway that links diet-derived amino acids to mitochondrial maintenance and energy output. Rather than broadly slowing protein recycling and causing a chronic buildup of damaged proteins, leucine seems to temporarily preserve "gateway" proteins, enabling mitochondria to import more enzymes and rapidly raise their energy output. Further experiments revealed that this "leucine pathway" may influence health more broadly. Worms carrying a mutation that disrupts leucine metabolism had fertility problems when this pathway was further disturbed, and human lung cancer cells with higher BCAA levels resisted drugs that block mitochondrial protein import.
These results come from short exposures in cultured human cells and worms, so it remains to be shown whether this pathway functions the same way in mammalian tissues at typical dietary leucine levels and what role it plays in health and disease. In Aliquot #114, I discuss supplements and dietary strategies to support mitochondrial function, and in Aliquot #115, I outline a lifestyle guide for mitochondrial optimization.