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. 2023 May 9;14:1121353. doi: 10.3389/fphys.2023.1121353

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Copyright © 2023 Song, Mao, Jing, Fu and Yan.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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NRF2/BACH1 pathway that regulates HO-1 expression. NRF2/MAFK heterodimers activate HO-1 expression. Activation of HO-1 expression is inhibited by BACH1/MAFK heterodimers at low heme concentrations. Meanwhile, NRF2 is polyubiquitinated and degraded by interacting with Kelch-like ECH-associated protein 1 (KEAP1) (left). At high heme concentrations, heme binds to BACH1. Then, BACH1 dissociates from MAF recognition elements (MARF), is exported to the cytoplasm and ubiquitinated for degradation. NRF2 nuclear accumulation via heme-mediated disruption of NRF2/KEAP1 complexes promotes the formation of NRF2/MAFK heterodimers (right). In this way, the NRF2/BACH1 pathway affects the expression of HO-1 and regulates heme homeostasis.