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. 2017 Dec 20;18(12):2772. doi: 10.3390/ijms18122772

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© 2017 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Positive feedback-loop of Nrf2 activation by p62/SQSTM1. (A) Domain structure of p62/SQSTM1; (B) p62/SQSTM1 is an important protein for selective autophagy, binds to Keap1 and other long-lived proteins and forms polyubiquitinated protein aggregates. Furthermore, it binds to the autophagy marker LC3 within the autophagosome, thereby leading the aggregated proteins into the autophagosome. After fusion with a lysosome, proteins and organelles, such as mitochondria, are degraded within the autophagosome. By binding to Keap1, p62/SQSTM1 stabilizes Nrf2 and enhances its translocation into the nucleus, where Nrf2 activates its target genes (↑ = upregulation of Nrf2 target genes). One of these genes is p62/SQSTM1.