Renu Wadhwa, Didik Priyandoko, Ran Gao, Nashi Widodo, Nupur Nigam, Ling Li, Hyo Min Ahn, Chae-Ok Yun, Nobuhiro Ando, Christian Mahe, Sunil C. Kaul
In order to identify the cellular factors involved in human melanogenesis, we carried out shRNA-mediated loss-of-function screening in conjunction with induction of melanogenesis by 1-oleoyl-2-acetyl-glycerol (OAG) in human melanoma cells using biochemical and visual assays. Gene targets of the shRNAs (that caused loss of OAG-induced melanogenesis) and their pathways, as determined by bioinformatics, revealed involvement of proteins that regulate cell stress response, mitochondrial functions, proliferation, and apoptosis. We demonstrate, for the first time, that the mitochondrial stress chaperone mortalin is crucial for melanogenesis. Upregulation of mortalin was closely associated with melanogenesis in in vitro cell-based assays and clinical samples of keloids with hyperpigmentation. Furthermore, its knockdown resulted in compromised melanogenesis. The data proposed mortalin as an important protein that may be targeted to manipulate pigmentation for cosmetic and related disease therapeutics. © 2016, Cell Stress Society International.
DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba, 305-8565, Ibaraki, Japan; Department of Biology, Universitas Pendidikan Indonesia, Bandung, Indonesia; Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, Indonesia; Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-Ro, Seongdong-Gu, Seoul, 133-791, South Korea; KK Chanel Research and Technology Development Laboratory, 1-1-5, Yamate, Funabashi-Chiba, 273-0045, Japan
