Autophagy is required for maintenance of amino acid levels and protein synthesis under nitrogen starvation

Autophagy is a transport system of cytoplasmic components to the lysosome/vacuole for degradation well conserved in eukaryotes. Autophagy is strongly induced by nutrient starvation. Several specific proteins, including amino acid synthesis enzymes and vacuolar enzymes, are increased during nitrogen starvation in wildtype cells but not in autophagy-defective Delta atg7 cells despite similar mRNA levels. We further examined deficiencies in these cells. Bulk protein synthesis was substantially reduced in Delta atg7 cells under nitrogen starvation compared with wild-type cells. The total intracellular amino acid pool was reduced in Delta atg7 cells, and the levels of several amino acids fell below critical values. In contrast, wild-type cells maintained amino acid levels compatible with life. Autophagy-defective cells fail to maintain physiologic amino acid levels, and their inability to synthesize new proteins may explain most phenotypes associated with autophagy mutants at least partly.