Stard1 promotes cholestatic liver injury and disease… : Hepatology
inly via the classic pathway and in a lower proportion through the mitochondrial acidic pathway. The latter requires STARD1-dependent cholesterol transport to the mitochondrial inner membrane for metabolism, whose contribution to BA-induced hepatotoxicity and CLD is unknown. Approach and Results: Here we show that patients with primary biliary cholangitis exhibit increased expression of STARD1 compared to control subjects. Mice with hepatocyte-specific Stard1 deletion (Stard1Δhep) were more resistant to experimental models of complete (bile duct ligation, BDL) and chemical obstructive cholestasis-induced liver injury, inflammation and fibrosis than Stard1f/f mice. Stard1Δhep mice exhibited reduced hepatic BAs and mitochondrial cholesterol accumulation but increased mitochondrial GSH (mGSH) levels following BDL compared to Stard1f/f mice. Pharmacological mGSH depletion sensitized primary mouse hepatocytes to a mix of BAs mimicking the profile seen in Stard1f/f mice after BDL leading to
