Peroxisome Membrane Protein PEX16 Inhibits Melanogenesis by Inhibiting the Wnt/β‐Catenin Signalling Pathway

Pigmented diseases can significantly impact people's quality of life, with melanogenesis playing a key role. In this study, we first analysed the relationship between peroxisomes, peroxisomal biogenesis factor 16 (PEX16), and melanin synthesis using omics data and clinical samples. Our results showed that peroxisome function and PEX16 expression were negatively associated with melanogenesis. Overexpression of PEX16 in the melanin-producing MNT1 cell line resulted in an increase in peroxisome production and the inhibition of key genes related to melanogenesis, such as microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerase (DCT). Consistently, when PEX16 was overexpressed in melanocytes, there was a significant reduction in melanin content. The expression of PEX16 was detected in skin tissues. We found that PEX16 expression was higher in the areas with relatively lower pigmentation and decreased following ultraviolet B (UVB) irradiation. Furthermore, our findings suggest that PEX16 can inhibit melanogenesis by suppressing the Wnt/β-catenin signalling pathway. In conclusion, PEX16 can inhibit the Wnt/β-catenin signalling pathway, thereby reducing melanogenesis. Our research provides new insights for the clinical diagnosis and treatment of skin pigmentation disorders.