Oligomerization of p 62 allows for selection of ubiquitinated cargo and isolation 1 membrane during selective autophagy 2 3

12 13 The authors declare that no competing interests exist. 14 2 Abstract 15 Autophagy is a major pathway for the clearance of harmful material from the cytoplasm. 16 During autophagy cytoplasmic material is delivered into the lysosomal system by organelles 17 called autophagosomes. Autophagosomes form in a de novo manner and, in the course of their 18 formation, isolate cargo material from the rest of the cytoplasm. Cargo specificity is conferred 19 by autophagic cargo receptors that selectively link the cargo to the autophagosomal 20 membrane decorated with ATG8 family proteins such as LC3B. Here we show that the human 21 cargo receptor p62/SQSTM-1 employs oligomerization to stabilize its interaction with LC3B 22 and linear ubiquitin when they are clustered on surfaces. Thus, oligomerization enables p62 23 to simultaneously select for the isolation membrane and the ubiquitinated cargo. We further 24 show in a fully reconstituted system that the interaction of p62 with ubiquitin and LC3B is 25 sufficient to bend the membrane around the cargo.