The role of ATP synthase subunit e (ATP5I) in mediating the metabolic and antiproliferative effects of metformin in cancer cells - PubMed
2 days ago
- #ATP5I
- #metformin
- #mitochondria
- ATP synthase subunit e (ATP5I) is identified as a target of metformin, affecting F₁F₀-ATP synthase dimer stability and cristae morphology.
- ATP5I knockout in pancreatic cancer cells mimics metformin effects: alters mitochondrial morphology, reduces NAD+/NADH ratio, inhibits OXPHOS, and increases glycolysis.
- Metformin disrupts F₁F₀-ATP synthase oligomerization, leading to vestigial assembly intermediates in cancer cells; ATP5I KO cells resist biguanide antiproliferative effects.
- Reintroducing ATP5I rescues metformin's metabolic and antiproliferative effects, and CRISPR screening links metformin to F₁F₀-ATP synthase inhibition, not complex I.