title: Autophagy has a significant role in determining skin color by regulating melanosome degradation in keratinocytes.
abstract: Melanin in the epidermis determines the wide variation in skin color associated with ethnic skin diversity. Ethnic differences exist regarding melanosome loss in keratinocytes, but the mechanisms underlying these differences, and their contribution to the regulation of skin color, remain unclear. Here, we explored the involvement of autophagy in determining skin color by regulating melanosome degradation in keratinocytes. Keratinocytes derived from Caucasian skin exhibit higher autophagic activity than those derived from African American (AA) skin. Furthermore, along with the higher autophagy activity in Caucasian skin-derived keratinocytes compared with AA skin-derived keratinocytes, Caucasian skin-derived keratinocytes were more sensitive to melanosome treatment as shown by their enhanced autophagic activity, which may reflect the substantial mechanisms in the human epidermis owing to the limitations of the models. Melanosome accumulation in keratinocytes was accelerated by treatment with lysosomal inhibitors or with small interfering RNAs specific for autophagy-related proteins, which are essential for autophagy. Furthermore, consistent with the alterations in skin appearance, the melanin levels in human skin cultured ex vivo and in human skin substitutes in vitro were substantially diminished by activators of autophagy and enhanced by the inhibitors. Taken together, our data reveal that autophagy has a pivotal role in skin color determination by regulating melanosome degradation in keratinocytes, and thereby contributes to the ethnic diversity of skin color.
authors.affiliation: Kao Biological Science Laboratories, Haga, Tochigi, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Murase
authors.affiliation: Kao Biological Science Laboratories, Haga, Tochigi, Japan. Electronic address: hachiya.akira@kao.co.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Hachiya
authors.affiliation: Kao Biological Science Laboratories, Haga, Tochigi, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Takano
authors.affiliation: Kao Biological Science Laboratories, Haga, Tochigi, Japan.
authors.forename: Rachel
authors.initials: R
authors.lastname: Hicks
authors.affiliation: Division of Plastic Surgery and Skin Sciences Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Marty O
authors.initials: MO
authors.lastname: Visscher
authors.affiliation: Kao Biological Science Laboratories, Haga, Tochigi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitahara
authors.affiliation: Kao Biological Science Laboratories, Haga, Tochigi, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hase
authors.affiliation: Research and Development Global, Kao, Sumida-ku, Tokyo, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Takema
authors.affiliation: Department of Genetics, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Yoshimori
mesh_terms: D000328:Adult; D001741:Black or African American; D001343:Autophagy / Q000502:physiology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005260:Female; D052816:Foreskin / Q000166:cytology; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D008545:Melanoma; D020460:Melanosomes / Q000378:metabolism*; D012878:Skin Neoplasms; D012880:Skin Pigmentation / Q000502:physiology*; D044465:White People