Article
KEAP1 retention in phase-separated p62 bodies drives liver damage under autophagy-deficient conditions.
EMBO reports - 1 Jul 2025
Takada Shuhei, Shinomiya Nozomi, Mao Gaoxin, Tsuchiya Hikaru, Koga Tomoaki, Komatsu-Hirota Satoko, Sou Yu-Shin, Abe Manabu, Ryzhii Elena, Suzuki Michitaka, Nakao Mitsuyoshi, Waguri Satoshi, Morishita Hideaki, Komatsu Masaaki
Abstract excerpt
Phase-separated p62 bodies activate NRF2, a key transcription factor for antioxidant response, by sequestering KEAP1, which targets NRF2 for degradation. Although p62 bodies containing KEAP1 are degraded by autophagy, they accumulate in various liver disorders. Their precise disease role remains unclear. We show that excessive KEAP1 retention in p62 bodies and NRF2 activation are major causes of liver damage when...
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