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. 2019 Oct 4;9:14354. doi: 10.1038/s41598-019-50877-8

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Schematic diagram showing the mechanism of Nrf2 activation by TFEB. TFEB first stabilizes Nrf2 through the repression of DCAF11, its E3 ubiquitin ligase, and activates Nrf2, resulting in the increased expression and phosphorylation of p62 at S349. Then, increased phosphorylated p62 disrupts the binding of Keap1 and Nrf2, thus leading to sustained Nrf2 activation through a positive feedback loop.