Following more than 50 years of mystery, scientists at the University of Cambridge have figured out how a molecular machine in our mitochondria works – and how inhibiting its function can help with certain conditions, including cancer and hair loss.
Indeed, the Medical Research Council (MRC) Mitochondrial Biology Unit team has uncovered the structure of this tiny machine inside the ‘powerhouses’ of our cells that help convert sugar into energy, according to a relatório by the University of Cambridge on April 18.
Furthermore, they have demonstrated how it operates like the lock on a canal to transport pyruvate, a molecule created in the body from the breakdown of sugars, into our mitochondria, hence its name – the mitochondrial pyruvate carrier.
To accomplish all this, the scientists have used a powerful technique called cryo-electron microscopy, which allowed them to magnify the mitochondrial pyruvate carrier to around 165,000 times its real size, allowing them to visualize its structure at the atomic level.
Like canal locks, but microscopic
First, the carrier passes through a gate on the outside of the mitochondria that opens to let pyruvate in. Then, that gate closes, and another gate on the inside opens to move the molecule through. As Professor Edmund Kunji from the MRC Mitochondrial Biology Unit, and a Fellow at Trinity Hall, Cambridge explained:
“It works like the locks on a canal but on the molecular scale. (…) There, a gate opens at one end, allowing the boat to enter. It then closes and the gate at the opposite end opens to allow the boat smooth transit through.”
A new target for fighting disease
Thanks to the key role of the carrier in how our cells generate energy, it has opened a range of opportunities for new treatments. Some diseases, like fatty liver disease or some cancers, rely heavily on pyruvate to fuel their cells, so blocking this carrier could help starve them and slow disease progression.
Surprisingly, it might also help with hair loss, as previous research suggests that blocking this carrier causes hair follicle cells to switch their energy source, which can actually promote hair growth.
With this new knowledge, scientists now have a clear image of how potential drugs might ‘jam’ the carrier – throwing a molecular spanner in the works – and pave the way for new treatments across a wide range of conditions. Notably, in the words of Professor Kunji:
“Drugs inhibiting the function of the carrier can remodel how mitochondria work, which can be beneficial in certain conditions. Electron microscopy allows us to visualize exactly how these drugs bind inside the carrier to jam it – a spanner in the works, you could say. This creates new opportunities for structure-based drug design in order to develop better, more targeted drugs. This will be a real game changer.”
Speaking of which, scientists have earlier this year discovered that pancreatic cancer specifically reprograms neurons for its own benefit and have managed to provide a detailed molecular analysis of the individual neurons in the tumors with reprogramed gene activity hindering cancer treatment.
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