Unlocking the Mitochondrial Gate: Scientists Reveal Structure Behind Key Cellular Energy Process.

In a major breakthrough, scientists at the University of Cambridge have finally unraveled the structure and function of a molecular machine inside our cells that plays a crucial role in energy production. This discovery could pave the way for new treatments targeting a range of health conditions, including cancer, metabolic disorders, and even hair loss.

For fifty years, researchers have known about a transporter in mitochondria—the energy-producing centers of cells—that is responsible for moving pyruvate, a key byproduct of sugar breakdown, into these organelles. However, until now, the precise structure and mechanism of this transporter, known as the mitochondrial pyruvate carrier (MPC), remained elusive.

Using advanced cryo-electron microscopy, a technique that enables visualization of biological structures at atomic resolution, the team led by the Medical Research Council (MRC) Mitochondrial Biology Unit was able to see how this tiny machine works. The findings, published in Science Advances, offer a detailed picture of how pyruvate is channeled into the mitochondria—essential for efficient energy production in the form of ATP, the cell’s energy currency.

Dr. Sotiria Tavoulari, a Senior Research Associate involved in the study, explained the significance of the carrier: “Sugars in our diet are broken down to form pyruvate. To generate the most energy from this molecule, it must be transported into mitochondria. This increases the cell's energy output by up to fifteen times.”

Maximilian Sichrovsky, a PhD student and co-lead author, highlighted how the team was able to not only visualize the MPC but also understand its function: “We found that it operates like a lock system in a canal. One gate opens to let pyruvate in, closes, and then another gate opens to release it inside the mitochondrion.”

Mitochondria have two membranes—the outer membrane allows pyruvate to pass through freely, while the inner membrane is selective. The MPC facilitates this inner passage, and its newly discovered structure shows a sophisticated gate-like mechanism regulating this transport.

Professor Edmund Kunji, a senior author on the study, described the analogy: “Think of it like canal locks—one end opens, then closes, and the opposite gate opens to let the boat through. In this case, the 'boat' is pyruvate.”

The implications of this discovery extend far beyond basic biology. Because the MPC plays a central role in cellular metabolism, it has become a target of interest for developing new therapies. Conditions like type 2 diabetes, fatty liver disease, and Parkinson’s disease could potentially be treated by modulating this transporter.

In some prostate cancers, cells overproduce MPCs to meet their high energy demands. Blocking this transport could effectively starve cancer cells by cutting off their primary fuel source. Similarly, in non-alcoholic fatty liver disease, preventing pyruvate from entering the mitochondria may force the body to metabolize excess fat stored in liver cells.

Interestingly, the MPC may also influence hair growth. Previous research has suggested that inhibiting the transporter in hair follicle cells leads to increased lactate production—a compound linked to hair regeneration.

“By jamming the transporter, we can reprogram mitochondrial function,” said Professor Kunji. “This gives us a powerful tool for designing drugs that can target specific cellular processes with precision.”

This groundbreaking work was made possible through collaboration with international experts from the Medical College of Wisconsin, the National Institutes of Health, and the Free University of Brussels. Supported by the Medical Research Council, this research represents a major step forward in our understanding of how cells harness energy and how this knowledge can be harnessed for therapeutic development.

Source:https://www.sciencedaily.com/releases/2025/04/250418235509.html

This is non-financial/medical advice and made using AI so could be wrong.