Regulation of autophagy by bile acids and in cholestasis - CholestoPHAGY or CholeSTOPagy.

ABSTRACT

Autophagy is a lysosomal degradation pathway in which the cell self-digests its own components to provide nutrients in harsh environmental conditions. It also represents an opportunity to rid the cell of superfluous and damaged organelles, misfolded proteins or invaded microorganisms. Liver autophagy contributes to basic hepatic functions such as lipid, glycogen and protein turnover. Deregulated hepatic autophagy has been linked to many liver diseases including alpha-1-antitrypsin deficiency, alcoholic and non-alcoholic fatty liver diseases, hepatitis B and C infections, liver fibrosis as well as liver cancer. Recently, bile acids and the bile acid receptor FXR have been implicated in the regulation of hepatic autophagy, which implies a role of autophagy also for cholestatic liver diseases. This review summarizes the current evidence of bile acid mediated effects on autophagy and how this affects cholestatic liver diseases. Although detailed studies are lacking, we suggest a concept that the activity of autophagy in cholestasis depends on the disease stage, where autophagy may be induced at early stages ("cholestophagy") but may be impaired in prolonged cholestatic states ("cholestopagy").