Figure - available from: Frontiers in Immunology
This content is subject to copyright.
The role of E3s and DUBs in NAFLD-related ERS, mitochondrial malfunction, and lipid autophagy. (1) E3 ubiquitin ligases CHIP and Nedd4L can ubiquitinate and degrade TXNIP in the endoplasmic reticulum stress pathway, inhibiting liver lipid deposition, inflammation, and fibrosis. TRIB3 recruits E3 ubiquitin ligase TRIM8 to degrade HNF4α and prevent NAFLD. E3 ubiquitin ligase Gp78 catalyzes the ubiquitination and degradation of unfolded proteins in the endoplasmic reticulum, relieving endoplasmic reticulum stress and inhibiting NASH and HCC. (2) The deubiquitinase USP14 deubiquitinates both FASN and HSP90AA1, boosting TG production and mitochondrial dysfunction, aggravating liver steatosis, inflammation, and fibrosis. Miz1, which promotes mitochondrial autophagy, can be degraded by ubiquitination, thereby inhibiting mitochondrial autophagy and exacerbating NASH. (3) HMGB1 promotes lipid autophagy, degrades lipid droplets, and helps to avoid NAFLD. In NAFLD, HMGB1 can be ubiquitinated and degraded by E3 ubiquitin ligase RNF186, thereby promoting the development of NAFLD.
Source publication
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and is closely associated with metabolic abnormalities. The causes of NAFLD are exceedingly complicated, and it is known that a variety of signaling pathways, endoplasmic reticulum stress, and mitochondrial dysfunction play a role in the pathogenesis of NAFLD....
