Pigment Cell & Melanoma Research 2014-11-01

Mitochondrial dynamics regulate melanogenesis through proteasomal degradation of MITF via ROS-ERK activation.

Eun Sung Kim, So Jung Park, Myeong-Jin Goh, Yong-Joo Na, Doo Sin Jo, Yoon Kyung Jo, Ji Hyun Shin, Eun Sun Choi, Hae-Kwang Lee, Ju-Yeon Kim, Hong Bae Jeon, Jin Cheon Kim, Dong-Hyung Cho

Index: Pigment Cell Melanoma Res. 27(6) , 1051-62, (2014)

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Abstract

Mitochondrial dynamics control mitochondrial functions as well as their morphology. However, the role of mitochondrial dynamics in melanogenesis is largely unknown. Here, we show that mitochondrial dynamics regulate melanogenesis by modulating the ROS-ERK signaling pathway. Genetic and chemical inhibition of Drp1, a mitochondrial fission protein, increased melanin production and mitochondrial elongation in melanocytes and melanoma cells. In contrast, down-regulation of OPA1, a mitochondria fusion regulator, suppressed melanogensis but induced massive mitochondrial fragmentation in hyperpigmented cells. Consistently, treatment with CCCP, a mitochondrial fission chemical inducer, also efficiently repressed melanogenesis. Furthermore, we found that ROS production and ERK phosphorylation were increased in cells with fragmented mitochondria. And inhibition of ROS or ERK suppressed the antimelanogenic effect of mitochondrial fission in α-MSH-treated cells. In addition, the activation of ROS-ERK pathway by mitochondrial fission induced phosphorylation of serine73 on MITF accelerating its proteasomal degradation. In conclusion, mitochondrial dynamics may regulate melanogenesis by modulating ROS-ERK signaling pathway. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.