Figure 1.

FOXO3 may act as a cell surveillance mechanism to maintain autophagy homeostasis. (left) Basal autophagy flux is upheld and homeostasis is maintained. FOXO3 is targeted for degradation by basal autophagy to confer low apoptosis sensitivity. (right) FOXO3 avoids autophagic turnover upon autophagy inhibition (genetic deletion of essential autophagy genes or pharmacological inhibition). FOXO3 transactivates autophagy-related genes and attempts to compensate for the perturbation in autophagy flux; if this correction is not achieved, FOXO3 leads to BBC3/PUMA transactivation and apoptosis sensitization.