Endolysosomal engulfment of autophagosomes independent of ESCRT

Endolysosomes, considered the cellular recycling compartments, receive and degrade materials from multiple pathways. However, whether endolysosomes can acquire cargo through alternative mechanisms remains unclear. Here, we identify a previously unrecognized endolysosomal pathway for material uptake. In this process, endolysosomes extend two membrane protrusions that envelop and ultimately engulf autophagosomes, independently of autophagosome-endolysosome fusion and the endosomal sorting complex required for transport complex (ESCRT)-mediated microautophagy. The endolysosomes containing internalized autophagosomes, acquire additional autophagosomes through homotypic fusion. A subset of autophagosomes is marked by F-actin on their membranes and the majority of them contain the ER protein Sec61β and the peroxisomal protein Pex16 within their lumens, whereas mitochondria remain excluded. Our discovery of this endolysosomal process unveils a previously uncharacterized pathway for cargo acquisition by endolysosomes.