After 50 years of mystery, researchers at the University of Cambridge have revealed how a molecular machine inside mitochondria enables cells to generate energy from sugars, a process crucial to all life on Earth. Using cryo-electron microscopy, the team uncovered the structure and function of the mitochondrial pyruvate carrier at the atomic scale.
This carrier transports pyruvate, a byproduct of sugar breakdown, into mitochondria—the cell’s powerhouse—where it helps boost energy production 15-fold in the form of ATP, the cellular fuel. The process is akin to canal locks: the carrier’s outer gate opens to admit pyruvate, closes, then opens an inner gate to release it into the mitochondrion.
Understanding this mechanism may lead to treatments for diabetes, fatty liver disease, Parkinson’s disease, certain cancers, and even hair loss.
Blocking the pyruvate carrier could redirect cells to alternative energy sources like fats or amino acids. This approach might treat fatty liver disease by utilizing harmful fat deposits in the liver or starve pyruvate-dependent cancer cells, like those in prostate cancer, by cutting off their energy supply.
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Potential applications extend to reversing hair loss by promoting lactate production in hair follicle cells when pyruvate entry is blocked.
Professor Edmund Kunji, who led the study, noted that understanding how this carrier works offers exciting opportunities for structure-based drug design. Cryo-electron microscopy has allowed researchers to visualize how drugs bind to the carrier, creating the potential for more effective, targeted therapies.
“This discovery opens the door to transformative advancements in medicine,” said Professor Kunji. “It’s a game-changer for understanding mitochondria and their role in health and disease.”
Journal Reference:
- Maximilian Sichrovsky et al., Molecular basis of pyruvate transport and inhibition of the human mitochondrial pyruvate carrier, Science Advances (2025). DOI: 10.1126/sciadv.adw1489
