FIGURE 2.

AMPK regulates autophagy through interaction with regulators of histone. AMPK inhibits H3K27me3 via direct phosphorylation of EZH2, which was reported to release TSC2 expression and then induce autophagy via inhibition of mTORC1. Under starvation conditions, AMPK can indirectly increase fumarate levels, leading to KDM2A repression, mTOR inhibition, and induction of autophagy. In addition, starvation-induced AMPK can regulate histone methylation through induction of autophagy via FOXO3 phosphorylation, transcriptional repression of SKP2, and nuclear translocation of CARM1, which directly interacts with TFEB, leading to induction of autophagy and lysosomal gene expression. P, phosphorylation; Me, methylation.