VDAC1 negatively regulates melanogenesis through the Ca²⁺-calcineurin-CRTC1-MITF pathway.

ABSTRACT: Melanocytes produce melanin for protecting DNA from ultraviolet exposure to maintain genomic stability. However, the precise regulation of melanogenesis is not fully understood. VDAC1, which is mainly localized in the outer mitochondrial membrane, functions as a gatekeeper for the entry or exit of Ca²⁺ between mitochondria and the cytosol and participates in multiple physiological processes. Here, we showed a novel role of VDAC1 in melanogenesis. Depletion of VDAC1 increased pigment content and up-regulated melanogenic genes, TYR, TYRP1, and TYRP2 Knockdown of VDAC1 increased free cytosolic Ca²⁺ in cultured melanocytes at the resting state, which activated calcineurin through the Ca²⁺-calmodulin-CaN pathway. The activated CaN dephosphor

SUBMITTER: Wang J 

PROVIDER: S-EPMC9160443 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature