Dynamic association of the ULK1 complex with omegasomes during autophagy induction

Abstract

Induction of autophagy requires the ULK1 protein kinase complex and the Vps34 lipid kinase complex. PI3P synthesised by Vps34 accumulates in omegasomes, membrane extensions of the ER within which some autophagosomes form, whereas the ULK1 complex is thought to target autophagosomes independently of PI3P, and its functional relation to omegasomes is unclear. Here we show that the ULK1 complex colocalizes with omegasomes in a PI3P-dependent way. Live imaging of Atg13 (a ULK1 complex component), omegasomes and LC3 establishes and annotates for the first time a complete sequence of steps leading to autophagosome formation as follows: Upon starvation, ULK1 complex forms puncta associated with the ER and sporadically with mitochondria. If PI3P is available, these puncta become omegasomes. Subsequently, the ULK1 complex exits omegasomes and autophagosomes bud off. If PI3P is unavailable, ULK1 puncta are greatly reduced in number and duration. Atg13 (a component of the ULK1 complex) contains a region with affinity for acidic phospholipids, required for translocation to punctate structures and autophagy progression.