Table 1.

The role of upstream pathway of mTOR-mediated autophagy in liver disease.

Liver Disease	Signaling Pathway	Effect	Target	Reference
Liver Fibrosis	PI3K/AKT/mTOR/autophagy	IGFBPrP1 promotes the activation of HSCs by activating PI3K/AKT/mTOR-mediated autophagy. MH, Rutin and Curcumin inhibit the activation of HSCs by activating PI3K/AKT/mTOR-mediated autophagy.	Inhibition of PI3K/AKT/mTOR- mediated autophagy Over-activation of PI3K/AKT/ mTOR-mediated autophagy	[153] [154,155]
Hepatitis B virus	PI3K/AKT/mTOR/autophagy	microRNA-99 family can promote replication of HBV by inducing PI3K/AKT/mTOR-mediated autophagy.	Inhibition of PI3K/AKT/mTOR- mediated autophagy	[157]
Non-alcoholic fatty liver disease	AMPK/mTOR/autophagy	LRG, FNDC5 and H2S activate AMPK/mTOR-mediated autophagy improve NAFLD. Acetaminophen inhibits AMPK/mTOR-mediated autophagy aggravating fat accumulation in NAFLD.	Activation of AMPK/mTOR- mediated autophagy	[201,202] [204] [207]
Liver ischemia and reperfusion	AMPK/mTOR/autophagy	Isoflurane activates AMPK/mTOR pathway mediated autophagy to improve hepatic ischemia-reperfusion injury. Inhibition of GSK3β can ameliorate hepatic ischemia-reperfusion injury by activating AMPK/mTOR-mediated autophagy.	Activation of AMPK/mTOR- mediated autophagy	[108] [212]
Liver Cancer	PI3K/AKT/mTOR/autophagy AMPK/mTOR/autophagy Ras/Raf/MEK/ERK/ mTOR/autophagy	Brusatol activates PI3K/AKT/mTOR-mediated autophagy of hepatoma cells, thereby effectively inducing apoptosis of hepatoma cells, inhibiting proliferation of hepatoma cells as well as invasion and migration of tumors. Bri and BCLB over-activate AMPK/mTOR-mediated autophagy to inhibit the growth and proliferation of hepatoma cells. Glycochenodeoxycholate activates AMPK/mTOR-mediated autophagy to promote hepatocellular carcinoma invasion and migration. RA-XII inhibits AMPK/mTOR-mediated autophagy to inhibit the growth and colony formation of HepG 2 cells. Bicyclol and AZA activate Ras/Raf/MEK/ERK/ mTOR-mediated autophagy to inhibit the proliferation of HepG2 or promote their senescence.	Over-activation of PI3K/AKT/ mTOR-mediated autophagy Over-activation of AMPK/mTOR- mediated autophagy Inhibition of AMPK/mTOR- mediated autophagy Activation of Ras/Raf/MEK/ERK/ mTOR-mediated autophagy	[167] [214,215] [217] [109] [242,243]