Abstract

Throughout their life, cells must maintain homeostasis while facing constantly fluctuating demands on their different organelles. A major mechanism for the homeostatic control of organelle function is the unfolded protein response (UPR), a signaling pathway that triggers a comprehensive remodeling of the endoplasmic reticulum (ER) and the biosynthetic pathway according to need. We discovered that activation of the UPR in yeast also induces a new branch of macroautophagy that selectively targets the ER. We term this process "ER-phagy", in analogy to pexophagy and mitophagy, the two other known forms of organelle-specific marcoautophagy. ER-phagy involves the generation of autophagosomes that selectively include ER membranes and whose delimiting double membranes also derive, at least in part, from the ER. This finding provides direct evidence that the ER can serve as a membrane source for autophagosome formation and indicates that ER-phagy entails engulfment of the ER by itself. ER-phagy could remove damaged or redundant parts of the ER and thus represent an important degradative functionality of the UPR that helps to afford homeostatic control. ©2007 Landes Bioscience.