Self-eating from an ER-associated cup

Abstract

Since the first morphological description of autophagosomes in the early 1960s, two critical questions have been a matter of intense investigation and debate: what is the origin of the autophagosomal membrane and how is it formed? A study by Axe et al. (E.L. Axe, S.A. Walker, M. Manifava, P. Chandra, H.L. Roderick, A. Habermann, G. Griffiths, and N.T. Ktistakis. 2008. J. Cell Biol. 182:685-701) provides evidence that cup-shaped protrusions from the endoplasmic reticulum, named omegasomes, serve as platforms for autophagosome biogenesis in mammalian cells.

Figure 1.

Proposed model for autophagosome formation from the ER. PI3P (red), generated by Vps34, marks the site for omegasome formation on the ER membrane by recruiting autophagic effectors. A cisterna expands and invaginates to form an omegasome, into which autophagic cargo is sequestered. Sequestered cargo is degraded when the resulting autophagosome fuses with a lysosome to form an autolysosome. Note that the nature of the cargo and the continuity of the omegasome with the ER membrane still remain to be established.