The Upstream Pathway of mTOR-Mediated Autophagy in Liver Diseases

Cells. 2019 Dec 9;8(12):1597. doi: 10.3390/cells8121597.


Autophagy, originally found in liver experiments, is a cellular process that degrades damaged organelle or protein aggregation. This process frees cells from various stress states is a cell survival mechanism under stress stimulation. It is now known that dysregulation of autophagy can cause many liver diseases. Therefore, how to properly regulate autophagy is the key to the treatment of liver injury. mechanistic target of rapamycin (mTOR)is the core hub regulating autophagy, which is subject to different upstream signaling pathways to regulate autophagy. This review summarizes three upstream pathways of mTOR: the phosphoinositide 3-kinase (PI3K)/protein kinase (AKT) signaling pathway, the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, and the rat sarcoma (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-extracellular activated protein kinase kinase (MEK)/ extracellular-signal-regulated kinase (ERK) signaling pathway, specifically explored their role in liver fibrosis, hepatitis B, non-alcoholic fatty liver, liver cancer, hepatic ischemia reperfusion and other liver diseases through the regulation of mTOR-mediated autophagy. Moreover, we also analyzed the crosstalk between these three pathways, aiming to find new targets for the treatment of human liver disease based on autophagy.

Keywords: AKT; AMPK; ERK; MEK; PI3K; Raf; Ras; autophagy; liver diseases; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy / genetics
  • Autophagy / physiology
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Liver Diseases / genetics
  • Liver Diseases / metabolism*
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology


  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase Kinases