Drosophila Atg7: Required for Stress Resistance, Longevity and Neuronal Homeostasis, but Not for Metamorphosis

Autophagy, the lysosomal degradation and recycling of self material, has been implicated in a number of developmental and pathological conditions including aging, cancer, neurodegeneration, and insect metamorphosis. Surprisingly, Atg7 mutant flies are able to complete metamorphosis with only a slight delay, despite strongly reduced autophagy levels. Similarly, developmental elimination of the larval midgut proceeds with normal morphology, suggesting that animals can compensate for reduced autophagy during development. Atg7 mutant adults are hypersensitive to starvation and oxidative stress, live shorter, and accumulate ubiquitin- positive aggregates in the brain that lead to a progressive decline of neuronal function and cell death. These results suggest that in Drosophila, normal levels of autophagy may play a more important role in the homeostasis of certain terminally differentiated cells and stress survival than during development.