Slimming down fat makes neuropathic hippo: the Fat/Hippo tumor suppressor pathway protects adult neurons through regulation of autophagy.

[]

Polyglutamine diseases are accompanied by large -scale alterations of transcription that may be responsible for neurodegeneration . We have monitored early transcriptional alterations in a Drosophila model for dentatorubral-pallidoluysian atrophy (DRPLA ) and reported the critical downregulation of the fat tumor suppressor gene . We show that , besides partially mediating neurodegeneration in the Drosophila model for DRPLA , fat and the downstream hippo pathway are essential for adult neuronal homeostasis . This function of the Fat /Hippo pathway is independent of the well-established actions on proliferation and cell polarity ; rather it has an impact upon autophagy , which is blocked and ineffective in fat /hippo mutants . These findings reveal the unexpected role in postmitotic neuronal homeostasis of a tumor suppressor pathway and hint at a new player involved directly or indirectly in the regulation of autophagy .