A conserved interplay between FOXO and SNAI/snail in autophagy.

Dysfunction of macroautophagy/autophagy has been implicated in homeostasis maintenance and contributes to various diseases. Yet the mechanisms that regulate autophagy have not been fully understood. In a recent study, we uncovered a coherent FOXO3-SNAI2 feed-forward regulatory loop in mammals that reinforces autophagy gene induction upon energy stress. Strikingly, a foxo-sna (snail) feed-forward circuit also exists in Drosophila , suggesting this regulating loop is evolutionarily conserved. Moreover, our results highlight that binding of FOXO3 to the DNA appears to be both necessary and sufficient to antagonize CRM1-dependent nuclear export, illustrating a critical role of DNA in regulating protein nuclear localization.