Autophagy-deficient tumor cells rely on extracellular amino acids to survive upon glutamine deprivation.

Macroautophagy/autophagy is a unique protein degradation process by which intracellular materials are recycled for energy homeostasis. However, the metabolic status and energy source of autophagy-defective tumor cells is poorly understood. Here in this study, we found ATF4-dependent amino acid transporter (AAT) gene expression and amino acid uptake were increased in autophagy-deficient cells under conditions of Gln deprivation. Notably, inhibition of amino acid uptake reduced the viability of Gln-deprived autophagy-deficient cells, but not significantly in wild-type cells, suggesting the reliance of autophagy-deficient tumor cells on extracellular amino acid uptake.