The FoxO-Autophagy Axis in Health and Disease

Autophagy controls cellular remodeling and quality control. Dysregulated autophagy has been implicated in several human diseases including obesity, diabetes, cardiovascular disease, neurodegenerative diseases, and cancer. Current evidence has revealed that FoxO (forkhead box class O) transcription factors have a multifaceted role in autophagy regulation and dysregulation. Nuclear FoxOs transactivate genes that control the formation of autophagosomes and their fusion with lysosomes. Independently of transactivation, cytosolic FoxO proteins induce autophagy by directly interacting with autophagy proteins. Autophagy is also controlled by FoxOs through epigenetic mechanisms. Moreover, FoxO proteins can be degraded directly or indirectly by autophagy. Cutting-edge evidence is reviewed that the FoxO-autophagy axis plays a crucial role in health and disease.