We report that autophagy-related gene 7 (ATG7) modulates p53 activity to regulate cell cycle and survival during metabolic stress, and that indicates Atg7 is functionally involved in cellular homeostasis in autophagy independent fashion. As a protein translation inhibitor, Programmed cell death 4 (PDCD4) expression is regulated by AKT1 phosphorylation. Here, we find that Atg7 interacts with PDCD4 and AKT1 to regulate AKT1-PDCD4 phosphorylation-ubiquitination axis during metabolic stress. We demonstrate that Atg7 senses decrease of ATP levels to suppress AKT-mediated PDCD4 phosphorylation at Ser67, which inhibits PDCD4 ubiquitinating during metabolic stress. Finally, PDCD4 accumulates and functions as a protein translation inhibitor to conserve energy, thus reducing apoptosis and allowing cells to survive stress periods. These results suggest that the ATP-Atg7-PDCD4 axis acts as a metabolic adaptation pathway which dictates cells to overcome metabolic stress.
This study reveals that ATG7, beyond its established role in autophagy, interacts with PDCD4 and AKT1 to regulate translation during metabolic stress. The ATG7PDCD4 axis operates as a metabolic adaptation pathway, conserving energy and fostering cell survival under stress.