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Mitochondrial dynamics regulate melanogenesis through proteasomal degradation of MITF via ROS ‐ ERK activation
Author(s) -
Kim Eun Sung,
Park So Jung,
Goh MyeongJin,
Na YongJoo,
Jo Doo Sin,
Jo Yoon Kyung,
Shin Ji Hyun,
Choi Eun Sun,
Lee HaeKwang,
Kim JuYeon,
Jeon Hong Bae,
Kim Jin Cheon,
Cho DongHyung
Publication year - 2014
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12298
Subject(s) - mitochondrial fission , microbiology and biotechnology , mapk/erk pathway , mitochondrion , mitochondrial ros , phosphorylation , chemistry , mitochondrial fusion , signal transduction , microphthalmia associated transcription factor , biology , mitochondrial dna , biochemistry , transcription factor , gene
Summary 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 D rp1, 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.