USP15 regulates p66Shc stability associated with Drp1 activation in liver ischemia/reperfusion.

ABSTRACT: Liver ischemia/reperfusion (I/R) injury is a major clinical concern of liver transplantation, which accounts for organ rejection and liver dysfunction. The adaptor protein p66Shc acts as a crucial redox enzyme and is implicated in liver I/R. Elevated p66Shc expression is associated with hepatocellular apoptosis in liver I/R, but the molecular mechanisms of p66Shc responsible for its aberrant expression and function remain unknown. In the present study, hepatocyte-specific p66Shc-knockdown mice exhibited clear inhibition in hepatocellular apoptosis and oxidative stress under liver I/R, while hepatocyte-specific p66Shc overexpression mice displayed the deteriorative impairment. Mechanistically, p66Shc-triggered mitochondrial fission and apoptosis in liver I/R by mediating ROS-driven Drp1 act

SUBMITTER: Tian X 

PROVIDER: S-EPMC9512921 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature