title: Stress chaperone mortalin regulates human melanogenesis.
abstract: 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.
authors.affiliation: DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan.
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
authors.affiliation: DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan.|Department of Biology, Universitas Pendidikan Indonesia, Bandung, Indonesia.
authors.forename: Didik
authors.initials: D
authors.lastname: Priyandoko
authors.affiliation: DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan.
authors.forename: Ran
authors.initials: R
authors.lastname: Gao
authors.affiliation: DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan.|Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, Indonesia.
authors.forename: Nashi
authors.initials: N
authors.lastname: Widodo
authors.affiliation: DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan.
authors.forename: Nupur
authors.initials: N
authors.lastname: Nigam
authors.affiliation: DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-Ro, Seongdong-Gu, Seoul, 133-791, South Korea.
authors.forename: Hyo Min
authors.initials: HM
authors.lastname: Ahn
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-Ro, Seongdong-Gu, Seoul, 133-791, South Korea.
authors.forename: Chae-Ok
authors.initials: CO
authors.lastname: Yun
authors.affiliation: KK Chanel Research and Technology Development Laboratory, 1-1-5, Yamate, Funabashi-Chiba, 273-0045, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ando
authors.affiliation: KK Chanel Research and Technology Development Laboratory, 1-1-5, Yamate, Funabashi-Chiba, 273-0045, Japan.
authors.forename: Christian
authors.initials: C
authors.lastname: Mahe
authors.affiliation: DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan. s-kaul@aist.go.jp.
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004075:Diglycerides / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D017495:Hyperpigmentation / Q000235:genetics*; D007627:Keloid / Q000235:genetics*; D008543:Melanins / Q000096:biosynthesis* / Q000235:genetics*; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012880:Skin Pigmentation / Q000235:genetics* / Q000502:physiology
chemical_list: D004075:Diglycerides; D018840:HSP70 Heat-Shock Proteins; C492001:HSPA9 protein, human; D008543:Melanins; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; C038237:1-oleoyl-2-acetylglycerol
keywords: Hsp60; Keloids; Melanogenesis; Regulation; Upregulation; mtHsp70/mortalin; shRNA screening