Metformin targets ATP synthase in cancer cells
Metformin has been the most prescribed type 2 diabetes drug for decades. New research now shows it also inhibits cancer cells through a specific component of the cell’s energy-producing machinery.
Researchers identified a protein called ATP5I as a target of metformin. ATP5I is a subunit of ATP synthase, the molecular complex that cells use to produce energy in mitochondria (the cell’s energy-producing organelles). This protein stabilises the ATP synthase structure and influences the shape of the inner membranes of mitochondria.
When ATP5I was disabled using CRISPR-Cas9 in pancreatic cancer cell lines, those cells displayed exactly the same behaviour as metformin-treated cells: altered mitochondrial shape and reduced capacity to proliferate. The study provides the first concrete molecular explanation for metformin’s anti-cancer effect.
Metformin as more than a diabetes drug
In the longevity field, metformin has long been viewed as a promising candidate. It extends lifespan in animals across multiple studies. The large TAME trial is currently underway to test whether it delays age-related diseases in humans.
But its exact mechanism of action remained unclear. It was already known that metformin acts on mitochondria. This research adds a specific protein to that picture. ATP5I is not only a target in pancreatic cancer; it plays a role in energy metabolism in nearly every cell type.
What this means going forward
Understanding that ATP5I connects metformin to its effects on cell division opens the door to more targeted therapies. Rather than metformin itself, with its broad systemic effects, future drugs could act specifically on ATP5I.
For now, the research confirms again that metformin is a pharmacologically richer compound than its modest reputation as a blood sugar lowering agent might suggest.