Small cell doorways can regenerate hair and fight cancer

After fifty years of scientific pursuit, researchers at the University of Cambridge have solved the mystery of the basic energy in our cells. Their work imagines for the first time how tiny pipe-like mechanisms shuttle important fuel molecules into mitochondria, converting sugar into cellular power chambers with available energy.

The study, published on April 18 in scientific development, reveals the atomic structure of a molecular machine called mitochondrial pyruvate carrier (MPC), which was first assumed in 1971 but remains structurally still until now.

“The sugars in our diet provide energy for the body to play. When they are partially dissolved within our cells, they produce pyruvate, but to make the most of the molecule, it needs to transfer it into the cell’s power chamber, the mitochondria.

The carrier operates like a miniature canal lock system, with the open and closed doors to transport pyruvate molecules on an otherwise impermeable internal mitochondrial membrane. This process allows cells to increase their energy production by 15 times.

“It works like a lock on a canal,” explained Professor Edmund Kunji of the MRC Mitochondrial Biology Unit. “There is a gate opened at one end to allow the ship to enter. Then close, the door at the other end can be opened to allow the ship to pass smoothly.”

The Cambridge team used a cryoelectron microscope to visualize the vector at nearly 165,000 times its actual size. This advanced imaging technology allows researchers to see not only the look of the carrier, but also how it works.

Maximilian Sichrovsky, a doctoral student who first author of the study, emphasized the importance of this structural insight: “It sounds simple to bring pyruvate into our mitochondria, but until now, we have not understood the mechanisms of this process.”

In addition to promoting basic biological knowledge, the research can open up new therapeutic avenues for a variety of diseases. Because the vector controls how mitochondria produces energy, it represents a promising drug target for diabetes, fatty liver disease, certain cancers, Parkinson’s disease and even hair loss.

“Pharmacists that inhibit carrier function can reshape the workings of mitochondria, which in some cases may be beneficial,” said Professor Kunji. For example, in fatty liver disease, blocking the carrier can force cells to metabolize stored liver fat. Likewise, some cancer cells, especially in prostate cancer, produce excess pyruvate vectors to promote their rapid growth, making the vector a potential target for starvation.

The study also explains how vectors are regulated by pH differences in mitochondrial membranes, which are a key factor in their transport function. Understanding these mechanical details provides new opportunities for designing targeted drugs that accurately control cellular metabolism.

This discovery ultimately led to decades of scientific research, providing a window for one of the most basic energy production mechanisms in life. The Cambridge team worked with researchers from the Wisconsin Medical School, the National Institutes of Health and the University of Brussels to complete the work.

For some tumors that rely heavily on pyruvate metabolism, disrupting the carrier may limit their energy supply. Likewise, inhibiting vectors in hair follicle cells may increase the production of lactic acid, thereby stimulating hair growth.

Detailed discovery has established a structural basis for the development of precisely targeted drugs that can address metabolic diseases with fewer side effects than currently treated. As Professor Kunji pointed out, this could be a “real game changer” in drug development.