La motilidad restringida por metformina de una línea celular de cáncer de pulmón activada por NRF2 implica el agotamiento de NAD+, en lugar de la señalización de AMPK o BACH1

assays upon treatment with metformin. However, depletion or overexpression of BACH1, or AMPK knockdown negated that metformin impaired cell migration primarily via BACH1 or AMPK. Metformin, as mitochondrial complex I inhibitor, increased the cellular NADH/NAD+ ratio. Supplementation with nicotinamide mononucleotide fueling NAD+ synthesis restored motility in metformin-treated cells. Thus, metformin administration does not seem to alleviate NRF2 activity but suppresses migration in KEAP1-deficient A549 cells. The latter is linked to NAD+ depletion, rather than AMPK activation or BACH1 downregulation.