We demonstrate that ATP5I interacts with a biguanide analogue in vitro, and disabling its expression by CRISPR-Cas9 in pancreatic cancer cells leads to the same phenotype as biguanide-treated cells, including mitochondrial morphology alterations, reduction of the NAD<sup>+</sup>/NADH ratio, inhibition of oxidative phosphorylation (OXPHOS), rescue of respiration by uncouplers, and a compensatory increase in glycolysis. The gene discussed is ATP5ME; the disease is familial pancreatic carcinoma.