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NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism

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dc.contributor.author이주희-
dc.date.accessioned2021-12-28T16:53:01Z-
dc.date.available2021-12-28T16:53:01Z-
dc.date.issued2021-08-
dc.identifier.issn0092-8674-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/186835-
dc.description.abstractUltraviolet (UV) light and incompletely understood genetic and epigenetic variations determine skin color. Here we describe an UV- and microphthalmia-associated transcription factor (MITF)-independent mechanism of skin pigmentation. Targeting the mitochondrial redox-regulating enzyme nicotinamide nucleotide transhydrogenase (NNT) resulted in cellular redox changes that affect tyrosinase degradation. These changes regulate melanosome maturation and, consequently, eumelanin levels and pigmentation. Topical application of small-molecule inhibitors yielded skin darkening in human skin, and mice with decreased NNT function displayed increased pigmentation. Additionally, genetic modification of NNT in zebrafish alters melanocytic pigmentation. Analysis of four diverse human cohorts revealed significant associations of skin color, tanning, and sun protection use with various single-nucleotide polymorphisms within NNT. NNT levels were independent of UVB irradiation and redox modulation. Individuals with postinflammatory hyperpigmentation or lentigines displayed decreased skin NNT levels, suggesting an NNT-driven, redox-dependent pigmentation mechanism that can be targeted with NNT-modifying topical drugs for medical and cosmetic purposes.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherCell Press-
dc.relation.isPartOfCELL-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleNNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Dermatology (피부과학교실)-
dc.contributor.googleauthorJennifer Allouche-
dc.contributor.googleauthorInbal Rachmin-
dc.contributor.googleauthorKaustubh Adhikari-
dc.contributor.googleauthorLuba M Pardo-
dc.contributor.googleauthorJu Hee Lee-
dc.contributor.googleauthorAlicia M McConnell-
dc.contributor.googleauthorShinichiro Kato-
dc.contributor.googleauthorShaohua Fan-
dc.contributor.googleauthorAkinori Kawakami-
dc.contributor.googleauthorYusuke Suita-
dc.contributor.googleauthorKazumasa Wakamatsu-
dc.contributor.googleauthorVivien Igras-
dc.contributor.googleauthorJianming Zhang-
dc.contributor.googleauthorPaula P Navarro-
dc.contributor.googleauthorCamila Makhlouta Lugo-
dc.contributor.googleauthorHaley R Noonan-
dc.contributor.googleauthorKathleen A Christie-
dc.contributor.googleauthorKaspar Itin-
dc.contributor.googleauthorNisma Mujahid-
dc.contributor.googleauthorJennifer A Lo-
dc.contributor.googleauthorChong Hyun Won-
dc.contributor.googleauthorConor L Evans-
dc.contributor.googleauthorQing Yu Weng-
dc.contributor.googleauthorHequn Wang-
dc.contributor.googleauthorSam Osseiran-
dc.contributor.googleauthorAlyssa Lovas-
dc.contributor.googleauthorIstván Németh-
dc.contributor.googleauthorAntonio Cozzio-
dc.contributor.googleauthorAlexander A Navarini-
dc.contributor.googleauthorJennifer J Hsiao-
dc.contributor.googleauthorNhu Nguyen-
dc.contributor.googleauthorLajos V Kemény-
dc.contributor.googleauthorOthon Iliopoulos-
dc.contributor.googleauthorCarola Berking-
dc.contributor.googleauthorThomas Ruzicka-
dc.contributor.googleauthorRolando Gonzalez-José-
dc.contributor.googleauthorMaria-Cátira Bortolini-
dc.contributor.googleauthorSamuel Canizales-Quinteros-
dc.contributor.googleauthorVictor Acuna-Alonso-
dc.contributor.googleauthorCarla Gallo-
dc.contributor.googleauthorGiovanni Poletti-
dc.contributor.googleauthorGabriel Bedoya-
dc.contributor.googleauthorFrancisco Rothhammer-
dc.contributor.googleauthorShosuke Ito-
dc.contributor.googleauthorMaria Vittoria Schiaffino-
dc.contributor.googleauthorLuke H Chao-
dc.contributor.googleauthorBenjamin P Kleinstiver-
dc.contributor.googleauthorSarah Tishkoff-
dc.contributor.googleauthorLeonard I Zon-
dc.contributor.googleauthorTamar Nijsten-
dc.contributor.googleauthorAndrés Ruiz-Linares-
dc.contributor.googleauthorDavid E Fisher-
dc.contributor.googleauthorElisabeth Roider-
dc.identifier.doi10.1016/j.cell.2021.06.022-
dc.contributor.localIdA03171-
dc.relation.journalcodeJ00472-
dc.identifier.eissn1097-4172-
dc.identifier.pmid34233163-
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0092867421007571-
dc.subject.keywordMITF-
dc.subject.keywordUVB-
dc.subject.keywordmelanosome-
dc.subject.keywordnicotinamide nucleotide transhydrogenase-
dc.subject.keywordpigmentation-
dc.subject.keywordredox regulation-
dc.contributor.alternativeNameLee, Ju Hee-
dc.contributor.affiliatedAuthor이주희-
dc.citation.volume184-
dc.citation.number16-
dc.citation.startPage4268-
dc.citation.endPage4283.e20-
dc.identifier.bibliographicCitationCELL, Vol.184(16) : 4268-4283.e20, 2021-08-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers

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