TOR-mediated autophagy regulates cell death in Drosophila neurodegenerative disease.

Publication Type:

Journal Article


The Journal of cell biology, Volume 186, Issue 5, p.703-11 (2009)


2009, Animals, Animals, Genetically Modified, Autophagy, Basic Sciences Division, Cell Death, Center-Authored Paper, Disease Models, Animal, Drosophila melanogaster, Drosophila Proteins, Electron Microscopy Core Facility, Flow Cytometry Core Facility, Monomeric GTP-Binding Proteins, Neurodegenerative Diseases, Neuropeptides, Phosphatidylinositol 3-Kinases, Photoreceptor Cells, Invertebrate, Protein Kinases, Protein-Serine-Threonine Kinases, Scientific Imaging Core Facility, Shared Resources, Signal Transduction


Target of rapamycin (TOR) signaling is a regulator of cell growth. TOR activity can also enhance cell death, and the TOR inhibitor rapamycin protects cells against proapoptotic stimuli. Autophagy, which can protect against cell death, is negatively regulated by TOR, and disruption of autophagy by mutation of Atg5 or Atg7 can lead to neurodegeneration. However, the implied functional connection between TOR signaling, autophagy, and cell death or degeneration has not been rigorously tested. Using the Drosophila melanogaster visual system, we show in this study that hyperactivation of TOR leads to photoreceptor cell death in an age- and light-dependent manner and that this is because of TOR's ability to suppress autophagy. We also find that genetically inhibiting TOR or inducing autophagy suppresses cell death in Drosophila models of Huntington's disease and phospholipase C (norpA)-mediated retinal degeneration. Thus, our data indicate that TOR induces cell death by suppressing autophagy and provide direct genetic evidence that autophagy alleviates cell death in several common types of neurodegenerative disease.