A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation

Autophagy is a bulk degradation process in eukaryotic cells and has fundamental roles in cellular homeostasis. The origin and source of autophagosomal membranes are long-standing questions in the field. Using electron microscopy, we show that, in mammalian culture cells, the endoplasmic reticulum ( ER) associates with early autophagic structures called isolation membranes (IMs). Overexpression of an Atg4B mutant, which causes defects in autophagosome formation, induces the accumulation of ER-IM complexes. Electron tomography revealed that the ER-IM complex appears as a subdomain of the ER that formed a cradle encircling the IM, and showed that both ER and isolation membranes are interconnected.