Endoplasmic Reticulum Stress Triggers Autophagy*

By Tomohiro Yorimitsu, Usha Nair, Zhifen Yang, D. Klionsky. Journal of Biological Chemistry, 2006

1,003 citations recorded by the source corpus.

Eukaryotic cells have evolved strategies to respond to stress conditions. For example, autophagy in yeast is primarily a response to the stress of nutrient limitation. Autophagy is a catabolic process for the degradation and recycling of cytosolic, long lived, or aggregated proteins and excess or defective organelles. In this study, we demonstrate a new pathway for the induction of autophagy. In the endoplasmic reticulum (ER), accumulation of misfolded proteins causes stress and activates the unfolded protein response to induce the expression of chaperones and proteins involved in the recovery process. ER stress stimulated the assembly of the pre-autophagosomal structure. In addition, autophagosome formation and transport to the vacuole were stimulated in an Atg protein-dependent manner. Finally, Atg1 kinase activity reflects both the nutritional status and autophagic state of the cell; starvation-induced autophagy results in increased Atg1 kinase activity. We found that Atg1 had high kinase activity during ER stress-induced autophagy. Together, these results indicate that ER stress can induce an autophagic response.

Subfields: Cell Biology, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/dd3c6622dbc356ead9aecc66019f9b4a9f472047

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. N. Mizushima
2. Peter Walter
3. M. Komatsu
4. T. Yoshimori
5. D. Ron
6. Tiziana Anelli
7. Roberto Sitia
8. Keiji Tanaka

In Epidemiology

1. N. Mizushima
2. Beth Levine
3. M. Komatsu
4. T. Yoshimori
5. Guido Kroemer
6. D. Klionsky
7. Xiao-Ming Yin
8. W. Ding

In Physiology

1. N. Mizushima
2. M. Komatsu
3. Xiao-Ming Yin
4. T. Yoshimori
5. W. Ding
6. M. Høyer-Hansen
7. Peter Walter
8. M. Jäättelä

Citations in the corpus

• Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium (2007, positive): “ER stress and autophagy was established in yeast Saccharomyces cerevisiae treated with distinct ER stressors, dithiothreitol that inhibits disulfide bond formation or tunicamycin that inhibits N-glycosylation.(19) The signaling pathway that”
• Loss of autophagy diminishes pancreatic beta cell mass and function with resultant hyperglycemia. (2008, background): “Other studies revealed important roles for auto- phagy in eradication of microbes, antigen presentation, tumor suppression (Levine and Kroemer, 2008), and endoplasmic retic- ulum (ER) stress responses (Yorimitsu et al., 2006; Ogata et al., 2006).”
• From Krebs to Clinic: Glutamine Metabolism to Cancer Therapy (2016, neutral): “BPTES inhibition of hGA(124-551), a truncated form of human kidneytype glutaminase.”
• Linking of autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability. (2007, background): “IRE1-mediated UPR is conserved in the yeast, in which ER stress could also induce autophagy.(21,24) IRE1 can activate a transcription factor, XBP-1, via its endoribonuclease activity,(27,28) and a stress kinase, JNK, via its association with TRAF2(29) and activation of a MAP3K, ASK-1.”
• Signal integration in the endoplasmic reticulum unfolded protein response (2007, background): “Many of the components that mediate autophagy have recently been identified as UPR target genes and are important for cells to survive severe ER stres”
• Self-eating and self-killing: crosstalk between autophagy and apoptosis (2007, background): “ER stress is also a particularly efficient stimulus of autophagy that specifically affects the ER (this is known as reticulophagy”