Figure 1.

Negative regulation of autophagy by SREBF1. Activation of CTH-H₂S signaling in the liver causes the sulfhydration of ULK1 at C951. This modification stabilizes the ULK1-ATG13-RB1CC1/FIP200 complex and increases its kinase activity in the autophagy initiation stage. However, the activation of SREBF1-Mir216a in a hepatic steatosis model inhibits CTH-H₂S signaling-mediated ULK1 sulfhydration, increasing UVRAG-RUBCN association, which blocks the fusion of autophagosomes with lysosomes. In contrast, SREBF1 deficiency leads to ULK1 sulfhydration-mediated autophagic flux, promoting lipid degradation and preventing hepatic steatosis