期刊
PIGMENT CELL & MELANOMA RESEARCH
卷 27, 期 6, 页码 1039-1050出版社
WILEY
DOI: 10.1111/pcmr.12297
关键词
mitochondrial dynamics; melanogenesis; Drp1; Opa1; ROS-ERK; MITF
资金
- JSPS Funding Program for Next Generation World-leading Researchers (NEXT Program)
- Grants-in-Aid for Scientific Research [25713037, 26115003] Funding Source: KAKEN
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 -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.
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