Journal
MOLECULAR ASPECTS OF MEDICINE
Volume 82, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.mam.2021.100973
Keywords
AALD; DILI; HCC; Lipophagy; Mitophagy; NAFLD
Funding
- National Institutes of Health [R37 AA020518, R01 DK102142, U01 AA024733, R01 AG072895, 1R21AG065720, DK117965, DK108835]
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The liver is a crucial metabolic organ, where autophagy plays a significant role in maintaining cellular and metabolic homeostasis. Autophagy in the liver fluctuates with hormonal cues, nutrient availability, and circadian activities. Dysfunctional autophagy may lead to various liver diseases.
The liver is a highly dynamic metabolic organ that plays critical roles in plasma protein synthesis, gluconeogenesis and glycogen storage, cholesterol metabolism and bile acid synthesis as well as drug/xenobiotic metabolism and detoxification. Research from the past decades indicate that autophagy, the cellular catabolic process mediated by lysosomes, plays an important role in maintaining cellular and metabolic homeostasis in the liver. Hepatic autophagy fluctuates with hormonal cues and the availability of nutrients that respond to fed and fasting states as well as circadian activities. Dysfunction of autophagy in liver parenchymal and non-parenchymal cells can lead to various liver diseases including non-alcoholic fatty liver diseases, alcohol associated liver disease, drug-induced liver injury, cholestasis, viral hepatitis and hepatocellular carcinoma. Therefore, targeting autophagy may be a potential strategy for treating these various liver diseases. In this review, we will discuss the current progress on the understanding of autophagy in liver physiology. We will also discuss several forms of selective autophagy in the liver and the molecular signaling pathways in regulating autophagy of different cell types and their implications in various liver diseases.
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