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

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Abstract
Autophagy is a bulk degradation process that takes place in specialized membrane structures, the origin of which is still unclear. An electron tomography study shows that the ER is connected to the isolation membranes that initiate autophagosome formation in mammalian cells, suggesting that the ER is the membrane source. 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.