Figure 8.

Molecular mechanism underlying impaired hepatic autophagy in G6PT deficiency. (A) G6PT deficiency leads to impaired hepatic autophagy that is mediated by downregulation of multiple autophagy-activating signaling pathways, including SIRT1/FoxO3a and LKB1/AMPK that lead to decreased expression of many components of the autophagy network, reduced autophagosome formation, increased p62 accumulation and attenuated autophagic flux. (B) Overexpression of either SIRT1 or LKB1 in G6PT-deficient liver upregulates both SIRT1/FoxO3a and LKB1/AMPK signaling and corrects impaired autophagy characterized by normalized expression of many components of the autophagy network, increased autophagosome formation and decreased p62 accumulation.