NADPH:Quinone Oxidoreductase-1 as a New Regulatory Enzyme That Increases Melanin Synthesis  Yuji Yamaguchi, Vincent J. Hearing, Akira Maeda, Akimichi Morita  Journal of Investigative Dermatology  Volume 130, Issue 3, Pages 645-647 (March 2010) DOI: 10.1038/jid.2009.378 Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Key players in melanin biosynthesis and NQO1 as an oxidoreductase that mediates the conversion of quinones to hydroquinones. Tyrosinase, DCT, and TYRP1 are enzymes that convert tyrosine (and DHI) to dopaquinone (and eumelanin), dopachrome to DHICA, and DHICA to eumelanin, respectively. Pheomelanin derives from dopaquinone based on the presence of cysteine. NQO1 is an oxidoreductase that mediates the conversion of quinones (including p-benzoquinone and coenzyme Q10) to hydroquinones (including narrowly defined hydroquinone and ubiquinol). DCT, dopachrome tautomerase; DHI, 5,6-dihydroxyindole; DHICA, 5,6-dihydroxyindole-2-carboxylic acid; NADPH, nicotinamide adenine dinuclueotide phosphate; NQO1, NADPH:quinone oxidoreductase-1; TYRP1, tyrosinase-related protein-1. Adapted from PubChem (http://pubchem.ncbi.nlm.nih.gov). Journal of Investigative Dermatology 2010 130, 645-647DOI: (10.1038/jid.2009.378) Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Scheme summarizing how NQO1 regulates melanin synthesis in melanocytes. NQO1 is regulated by ARE, which is enhanced by Nrf2. Nrf2 migrates into the nucleus from the cytoplasm, where it is released from Keap1 in response to various stimuli. NQO1 does not significantly affect the expression of MITF, TYRP1, or DCT, but it increases the catalytic activity and protein level of tyrosinase and thereby induces melanin synthesis. Vertical blue arrows indicate up- or downregulation in response to NQO1 stimulation; horizontal blue arrow indicates that NQO1 stimulation has no effect on DCT expression. Blue labels indicate data presented by Choi et al. (2010). ARE, antioxidant response element; DCT, dopachrome tautomerase; Keap1, Kelch-like ECH-associated protein-1; MITF, microphthalmia-associated transcription factor; NQO1, NADPH:quinone oxidoreductase-1; Nrf2, an NF-E2 family of nuclear basic leucine zipper transcription factors; TYRP1, tyrosinase-related protein-1. Journal of Investigative Dermatology 2010 130, 645-647DOI: (10.1038/jid.2009.378) Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

Journal of Investigative Dermatology 2010 130, 645-647DOI: (10 Journal of Investigative Dermatology 2010 130, 645-647DOI: (10.1038/jid.2009.378) Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions