Atg1‐independent induction of autophagy by the Drosophila Ulk3 homolog, ADUK

Although canonical autophagy regulation requires a multi‐protein complex centered on the Ser/Thr‐kinase Atg1 (mammalian Ulk1/2), alternative signals can induce autophagy independent of Atg1 through unknown mechanisms. Here we identify the Drosophila Ulk3 ortholog, another Drosophila Unc‐51‐like kinase (ADUK), as an Atg1‐independent autophagy inducer. ADUK interacts with Atg1 complex members Atg13 and 200 kDa FAK family kinase‐interacting protein, and requires Atg13 but not Atg1 for autophagy induction. Loss of ADUK shortens adult lifespan and reduces the autophagic response to a chemical stressor, dimethyl sulfoxide. However, ADUK is not required for autophagy induction by Atg1‐dependent nutrient or developmental cues. Atg1 and ADUK/Ulk3 thus represent alternative catalytic components of a shared autophagy kinase complex. The induction of autophagy in response to starvation or other cellular stressors is orchestrated by the kinase Atg1 (called Ulk1/2 in humans and other mammals). Atg1‐independent autophagy has been previously reported, but the mechanisms remain elusive. In this report, Braden and Neufeld identify the Drosophila Ulk family kinase ADUK as a Ulk3 orthologue that can promote autophagy in the absence of Atg1 via interactions with the Atg1 complex members FIP200 and Atg13. Despite sharing these factors with Atg1, ADUK is dispensable for starvation‐induced autophagy, but is required for autophagy induction by chemical stress.