Autophagy, a degradative pathway for removal of cytoplasmic proteins and organelles through sequestration in autophagosomes and lysosomal degradation, has been suggested to be important for embryonic development. Rubinsztein and colleagues report in Nature Communications (http://doi.org/jrd) that autophagy can be controlled by the Hedgehog (HH) signalling pathway in mammalian cells and in Drosophila melanogaster.

Activation of HH signalling by a variety of means impairs autophagy; specifically, autophagosome formation. Known components of the HH signalling pathway — the receptors PTCH1 and PTCH2, the transmembrane protein SMO (which acts downstream of the receptors) and the transcription factor GLI2 in mammalian cells — are also required for HH effects on autophagy. Regulation of autophagy by the HH pathway was also conserved in Drosophila. In an effort to identify downstream targets of HH signalling that may directly modulate autophagy, the authors assessed changes in the expression patterns of an array of autophagy genes in response to HH signalling activation. They found that PERK (also known as EIF2AK3) and GABARAP1, both implicated in autophagy, were reduced following HH activation; however, additional effectors were also likely to be implicated in autophagy regulation by the HH pathway. The mechanistic details of how the HH pathway controls autophagy await future study.