Abstract
Alcohol-related liver disease (ALD) is caused by over-consumption of alcohol. ALD can develop a spectrum of pathological changes in the liver, including steatosis, inflammation, cirrhosis, and complications. Autophagy is critical to maintain liver homeostasis, but dysfunction of autophagy has been observed in ALD. Generally, autophagy is considered to protect the liver from alcohol-induced injury and steatosis. In this review, we will summarize novel modulators of autophagy in hepatic metabolism and ALD, including autophagy-mediating non-coding RNAs (ncRNAs), and crosstalk of autophagy machinery and nuclear factors. We will also discuss novel functions of autophagy in hepatocytes and non-parenchymal hepatic cells during the pathogenesis of ALD and other liver diseases.
Highlights
Over-consumption of alcohol can cause a spectrum of alcohol-related liver disease (ALD) including alcoholic fatty liver disease, alcoholic hepatitis, cirrhosis, and complications [1]
In order to demonstrate the function of TFEB in ALD, the authors first knocked down hepatic Tfeb by shRNA in mice and found that TFEB knockdown exacerbated liver injury and steatosis induced by chronic-plus-binge alcohol treatment
Current studies have confirmed that autophagy is critical to normal liver functions, and dysfunction of autophagy contributes to the pathogenesis of various liver diseases, including ALD
Summary
Over-consumption of alcohol can cause a spectrum of alcohol-related liver disease (ALD) including alcoholic fatty liver disease, alcoholic hepatitis, cirrhosis, and complications [1]. CMA is mediated by chaperones, e.g., heat shock-cognate protein of 70 kDa (HSC70), and specific protein targets are shuttled via the chaperones across the lysosomal membrane for degradation in the lumen [11]. Among these three types of autophagic process, macroautophagy, referred to hereafter as autophagy, is the most active form and has been widely studied in liver physiology and diseases. Multiple mechanisms are involved in this induction, including ethanol metabolites (mostly acetaldehyde) [15], ROS [14,16], and alteration of signaling pathways (such as the mammalian target of rapamycin (mTOR), 5 AMP-activated protein kinase (AMPK), and forkhead box O (FOXO)3a pathways) [17,18,19,20]. We will summarize new findings regarding the signaling and roles of the macroautophagic process in ALD, focusing on novel factors that have been shown to mediate autophagy during the pathogenesis of ALD
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