Dynamin-2 controls phagophore maturation

Abstract

Autophagy involves rapid growth of phagophores through membrane addition. Newly added membranes are derived from other organelles through vesicles carrying the Atg9 protein. Membrane is delivered by fusing these vesicles with the phagophores. Atg9 is, nevertheless, not incorporated in autophagosomes. We now show that this protein is retrieved from phagophores by fission utilizing Dynamin-2 (Dnm2) as the membrane scission protein. Blocking Atg9 recycling by interfering with Dnm2 helps retain Atg9 in autophagosomes and degrades this protein by autophagy. Dnm2 colocalizes with the BAR domain protein Endophilin-B1 (EndoB1/Bif-1) when autophagy is induced, consistent with transient interactions during Atg9 retrieval. EndoB1 and Dnm2 also control the downstream fusion of phagophores to late endosomes, thus ensuring the completion of phagophores before proceeding to the next stage in the autophagy process. These data provide novel insights into the roles of membrane scission proteins during autophagy.