Fig. 9

Ufl1 and Ufbp1-dependent-UFMylation acts in a protective role in maintaining liver homeostasis. Aberrant upregulation of p-mTOR and GβL results from Ufl1 and Ufbp1 deficiency in the liver, which also leads strongly to p70S6K and 4EBP1 phosphorylation. The chronic and abnormal activation of mTOR signaling pathway results in the accumulation of misfolded proteins, which induces liver damage. Hepatocyte steatosis and fibrosis occur in Ufl1^Δ/Δhep and Ufbp1^Δ/Δhep mice at the age of 6–8 weeks initially. Ballooning and steatohepatitis develop at 8-month-old, and more than a half of Ufl1^Δ/Δhep mice develop liver cancer at about 14-month-old. The mTOR inhibitor rapamycin attenuates the extent of hepatic steatosis partially through inhibiting the mTOR signaling pathway