Electron Tomographic Analysis of Autophagosome Formation

Abstract

Autophagy is a bulk degradation process in eukaryotic cells. Increasing evidence suggest that autophagy has diverse physiological functions, including starvation adaptation, development, immunity, tumor suppression, and cell death. The origin and source of autophagosomal membranes are long-standing questions in the field. Using electron microscopy, we show that the endoplasmic reticulum (ER) associates with early autophagic structures called isolation membranes (IM) in mammalian culture cells. Electron tomography revealed that the ER-associated IM appears as a subdomain of the ER that formed a cradle encircling the IM, and showed that both ER and isolation membranes were interconnected. Our results suggested that autophagosomal membrane originate from ER subdomains, and the ER is a membrane souse for autophagosome formation.