510 NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism

While the UV-MITF pathway is well-established as a key player of pigmentation, implication other MITF independent pathways in this biological process still unclear. Illustrating this, several evidence demonstrated role oxidative stress pigmentation disorders but exact mechanisms by which potentially impacts skin are incompletely elucidated. Here, we identified conserved mechanism demonstrating an interplay between melanin and redox metabolism. In study, showed that enzyme nicotinamide nucleotide transhydrogenase (NNT), involved regulation stress, could be also implicated melanogenesis. By loss gain function experiments using pharmacological compounds, NNT-mediated changes impact mice zebrafish models well ex vivo human explants. At mechanistic level, have shown loss-of-function affects ubiquitin-proteasome-mediated tyrosinase degradation, synthesis. Finally, to study relevance these findings humans, GWAS analysis was performed databases 462, 885 individuals total. Four SNP within NNT gene were found significantly correlate with color. addition, therapeutic potential NNT-modifying topical drugs on explants different types. Altogether, results highlight existence redox-dependent can targeted for cosmetic medical purposes.