Boosting mitochondria activity by silencing MCJ overcomes cholestasis-induced liver injury

•Hepatic MCJ levels were upregulated in patients with cholestatic liver disease.•MCJ absence resulted in decreased liver inflammation, neutrophil activation, and mitochondrial dysfunction after BDL.•MCJ deficiency protected the hepatocytes from ROS overproduction and ATP depletion.•In vivo inhibition of MCJ expression mitigated liver injury by bile acids.•Our results identified MCJ as a key regulator of cholestatic liver disease.