Bile acid regulation of the autophagy-lysosome axis. (IMAGE)
Caption
Autophagy is a lysosome-dependent cellular degradation pathway that plays a key role in cellular nutrient homeostasis, organelle homeostasis and lipid homeostasis. Transcription factor EB (TFEB) is a nutrient and stress-sensing transcriptional factor that is activated in response to nutrient starvation and lysosome stress. In turn, TFEB induced genes that promote autophagy and lysosome biogenesis. Postprandial circulating bile acids and fibroblast growth factor 15 or 19 (FGF15/19) increase in response to food intake. Bile acids activated hepatic farnesoid X receptor (FXR) represses autophagy genes. In addition, FGF15/19 signalling inhibits TFEB nuclear translocation via activating intracellular mechanistic target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signalling. As a result, bile acids contribute to the postprandial repression of the hepatic autophagy-lysosome axis. In cholestasis, bile acid accumulation may contribute to impaired hepatic autophagy-lysosome axis, which in turn exacerbates cellular dysfunction and injury in hepatocytes.
Credit
By Tiangang Li, Mohammad Nazmul Hasan, Lijie Gu.
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License
CC BY-NC