NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism.
- Allouche Jennifer
- Rachmin Inbal
- Adhikari Kaustubh
- Pardo Luba M.
- Lee Ju Hee
- McConnell Alicia M.
- Kato Shinichiro
- Fan Shaohua
- Kawakami Akinori
- Suita Yusuke
- Wakamatsu Kazumasa
- Igras Vivien
- Zhang Jianming
- Navarro Paula P.
- Lugo Camila Makhlouta
- Noonan Haley R.
- Christie Kathleen A.
- Itin Kaspar
- Mujahid Nisma
- Lo Jennifer A.
- Won Chong Hyun
- Evans Conor L.
- Weng Qing Yu
- Wang Hequn
- Osseiran Sam
- Lovas Alyssa
- Németh István Balázs
- Cozzio Antonio
- Navarini Alexander A.
- Hsiao Jennifer J.
- Nguyen Nhu
- Kemény Lajos V.
- Iliopoulos Othon
- Berking Carola
- Ruzicka Thomas
- Gonzalez-Jose ́ Rolando
- Bortolini Maria-Cátira
- Canizales-Quinteros Samuel
- Acuna-Alonso Victor
- Gallo Carla
- Poletti Giovanni
- Bedoya Gabriel
- Rothhammer Francisco
- Ito Shosuke
- Schiaffino Maria Vittoria
- Chao Luke H.
- Kleinstiver Benjamin P.
- Tishkoff Sarah
- Zon Leonard I.
- Nijsten Tamar
- Ruiz-Linares Andrés
- Fisher David E.
- Roider Elisabeth Maria
DOIAbstract
Ultraviolet (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. An...
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