SIRT7-mediated NRF2 deacetylation promotes antioxidant response and protects against chemodrug-induced liver injury.

ABSTRACT: NRF2 has been recognized as a central hub that neutralizes ROS and restores intracellular redox balance. In addition to KEAP1 mediated ubiquitin-proteasome degradation, post-translational modifications of NRF2 are critical for regulating its nuclear translocation and activation but precise mechanisms underly this regulation remain elusive. In this study, we found that SIRT7 was sufficient and essential for NRF2 nuclear localization and activation. Knockdown of SIRT7 significantly impaired intercellular ROS homeostasis and increased apoptosis in response to oxidative stress including chemodrug treatment. SIRT7 interacted with NRF2 and induced its deacetylation, by which inhibited binding of NRF2 to KEAP1, enhanced NRF2 protein stability and promoted its nuclear translocation. SIRT7 induced

SUBMITTER: Yu T 

PROVIDER: S-EPMC11961749 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature