COMMD3 Mediates Melanin Synthesis through both Clusterin-PAX3 Axis and Copper-Dependent Tyrosinase Activity in Skin Pigmentation

Xinyi Huang

doi:10.1016/j.jdermsci.2026.04.005

COMMD3 Mediates Melanin Synthesis through both Clusterin-PAX3 Axis and Copper-Dependent Tyrosinase Activity in Skin Pigmentation

2026-04-30

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AI

X

Xinyi Huang

S

Shan Wu

M

Min Yan

S

Shengzhe Zhou

J

Jiadie Wang

J

Jianghan Li

M

Min Yao *

DOI：10.1016/j.jdermsci.2026.04.005

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• UVB exposure leads to COMMD3 increase in pigmented B16F10 cells and murine models. COMMD3 deficiency reduces melanin synthesis via copper accumulation, especially accumulation of Cu(I), which increases the proportion of inactive tyrosinase. • Clusterin increases in response to copper alteration caused by COMMD3 deficiency to reduce PAX3 nuclear translocation for further MITF activation, which regulates skin melanogenesis and pigmentation. • Our study implies a potential treatment of controlling COMMD3 expression and copper levels for restoring normal physiological skin pigmentation.

Keywords:

COMMD3

melanin synthesis

copper

tyrosinase

Clusterin

COMMD3 Mediates Melanin Synthesis through both Clusterin-PAX3 Axis and Copper-Dependent Tyrosinase Activity in Skin Pigmentation

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