Talk:Cell Death 1
Autophagy Counterbalances Endoplasmic Reticulum Expansion during the Unfolded Protein Response
The protein folding capacity of the endoplasmic reticulum (ER) is regulated by the unfolded protein response (UPR). The UPR senses unfolded proteins in the ER lumen and transmits that information to the cell nucleus, where it drives a transcriptional program that is tailored to re-establish homeostasis. Using thin section electron microscopy, we found that yeast cells expand their ER volume at least 5-fold under UPR-inducing conditions. Surprisingly, we discovered that ER proliferation is accompanied by the formation of autophagosome-like structures that are densely and selectively packed with membrane stacks derived from the UPR-expanded ER. In analogy to pexophagy and mitophagy, which are autophagic processes that selectively sequester and degrade peroxisomes and mitochondria, the ER-specific autophagic process described utilizes several autophagy genes: they are induced by the UPR and are essential for the survival of cells subjected to severe ER stress. Intriguingly, cell survival does not require vacuolar proteases, indicating that ER sequestration into autophagosome-like structures, rather than their degradation, is the important step. Selective ER sequestration may help cells to maintain a new steady-state level of ER abundance even in the face of continuously accumulating unfolded proteins.
Citation: Bernales S, McDonald KL, Walter P (2006) Autophagy Counterbalances Endoplasmic Reticulum Expansion during the Unfolded Protein Response. PLoS Biol 4(12): e423. doi:10.1371/journal.pbio.0040423
Academic Editor: Hidde Ploegh, Massachusetts Institute of Technology, United States of America
Received: May 25, 2006; Accepted: October 11, 2006; Published: November 28, 2006
Copyright: © 2006 Bernales et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by an American Heart Predoctoral Fellowship to SB and by grants from the National Institutes of Health to PW. PW is an Investigator of the Howard Hughes Medical Institute.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: A1PiZ, Z variant of human α-1 proteinase inhibitor; Cvt, cytoplasm-to-vacuole targeting; EM, electron microscopy; ER, endoplasmic reticulum; ERA, ER-containing autophagosome; ERAD, ER-associated protein degradation; ER-phagy, ER-selective branch of autophagy; GFP, green fluorescent protein; NE, nuclear envelope; PAS, pre-autophagosomal structure; S-UPR, Super-unfolded protein response; UPR, unfolded protein response