Faculty Opinions recommendation of Substrate-specific translocational attenuation during ER stress defines a pre-emptive quality control pathway.

2006 ◽  
Author(s):  
Martin Pool
Keyword(s):  
Quality Control ◽  
Er Stress

scholarly journals Activation of Mammalian Unfolded Protein Response Is Compatible with the Quality Control System Operating in the Endoplasmic Reticulum

2004 ◽  
Vol 15 (6) ◽  
pp. 2537-2548 ◽  
Author(s):  
Satomi Nadanaka ◽  
Hiderou Yoshida ◽  
Fumi Kano ◽  
Masayuki Murata ◽  
Kazutoshi Mori
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Control System ◽  
Golgi Apparatus ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Secretory Pathway ◽  
Unfolded Proteins ◽  
Unfolded Protein ◽  
Protein Response

Newly synthesized secretory and transmembrane proteins are folded and assembled in the endoplasmic reticulum (ER) where an efficient quality control system operates so that only correctly folded molecules are allowed to move along the secretory pathway. The productive folding process in the ER has been thought to be supported by the unfolded protein response (UPR), which is activated by the accumulation of unfolded proteins in the ER. However, a dilemma has emerged; activation of ATF6, a key regulator of mammalian UPR, requires intracellular transport from the ER to the Golgi apparatus. This suggests that unfolded proteins might be leaked from the ER together with ATF6 in response to ER stress, exhibiting proteotoxicity in the secretory pathway. We show here that ATF6 and correctly folded proteins are transported to the Golgi apparatus via the same route and by the same mechanism under conditions of ER stress, whereas unfolded proteins are retained in the ER. Thus, activation of the UPR is compatible with the quality control in the ER and the ER possesses a remarkable ability to select proteins to be transported in mammalian cells in marked contrast to yeast cells, which actively utilize intracellular traffic to deal with unfolded proteins accumulated in the ER.

scholarly journals Molecular mechanism of ER stress-induced pre-emptive quality control involving association of the translocon, Derlin-1, and HRD1

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Hisae Kadowaki ◽  
Pasjan Satrimafitrah ◽  
Yasunari Takami ◽  
Hideki Nishitoh
Keyword(s):  
Quality Control ◽  
Er Stress ◽  
Molecular Mechanism

scholarly journals A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress

2020 ◽  
Author(s):  
Madlen Stephani ◽  
Lorenzo Picchianti ◽  
Alexander Gajic ◽  
Rebecca Beveridge ◽  
Emilio Skarwan ◽  
...  
Keyword(s):  
Quality Control ◽  
Er Stress ◽  
Mammalian Cells ◽  
Control Mechanisms ◽  
Receptor Complex ◽  
Er Quality Control ◽  
Proteotoxic Stress ◽  
Binding Epitope ◽  
Quality Control Mechanism ◽  
Passenger Proteins

SummaryEukaryotes have evolved various quality control mechanisms to promote proteostasis in the ER. Selective removal of certain ER domains via autophagy (termed as ER-phagy) has emerged as a major quality control mechanism. However, the degree to which ER-phagy is employed by other branches of ER-quality control remains largely elusive. Here, we identify a cytosolic protein, C53, that is specifically recruited to autophagosomes during ER-stress, in both plant and mammalian cells. C53 interacts with ATG8 via a distinct binding epitope, featuring a shuffled ATG8 interacting motif (sAIM). C53 senses proteotoxic stress in the ER lumen by forming a tripartite receptor complex with the ER-associated ufmylation ligase UFL1 and its membrane adaptor DDRGK1. The C53/UFL1/DDRGK1 receptor complex is activated by stalled ribosomes and induces the degradation of internal or passenger proteins in the ER. Consistently, the C53 receptor complex and ufmylation mutants are highly susceptible to ER stress. Thus, C53 forms an ancient quality control pathway that bridges selective autophagy with ribosome-associated quality control at the ER.

scholarly journals Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) and Their Prospective Roles in Kidney Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-21
Author(s):  
Peng Gao ◽  
Wenxia Yang ◽  
Lin Sun
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Kidney Disease ◽  
Er Stress ◽  
Future Research ◽  
Inflammasome Activation ◽  
Mitochondrial Quality Control ◽  
Downstream Signaling ◽  
Contact Sites ◽  
Progression Of Kidney Disease

Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) serve as essential hubs for interorganelle communication in eukaryotic cells and play multifunctional roles in various biological pathways. A defect in ER-mitochondria signaling or MAMs dysfunction has pleiotropic effects on a variety of intracellular events, which results in disturbances of the mitochondrial quality control system, Ca2+ dyshomeostasis, apoptosis, ER stress, and inflammasome activation, which all contribute to the onset and progression of kidney disease. Here, we review the structure and molecular compositions of MAMs as well as the experimental methods used to study these interorganellar contact sites. We will specifically summarize the downstream signaling pathways regulated by MAMs, mainly focusing on mitochondrial quality control, oxidative stress, ER-mitochondria Ca2+ crosstalk, apoptosis, inflammasome activation, and ER stress. Finally, we will discuss how alterations in MAMs integrity contribute to the pathogenesis of kidney disease and offer directions for future research.

scholarly journals Possible involvement of endoplasmic reticulum stress in the pathogenesis of Alzheimer’s disease

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Toru Hosoi ◽  
Jun Nomura ◽  
Koichiro Ozawa ◽  
Akinori Nishi ◽  
Yasuyuki Nomura
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Protein Quality ◽  
Unfolded Proteins ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

AbstractThe endoplasmic reticulum (ER) is an organelle that plays a crucial role in protein quality control such as protein folding. Evidence to indicate the involvement of ER in maintaining cellular homeostasis is increasing. However, when cells are exposed to stressful conditions, which perturb ER function, unfolded proteins accumulate leading to ER stress. Cells then activate the unfolded protein response (UPR) to cope with this stressful condition. In the present review, we will discuss and summarize recent advances in research on the basic mechanisms of the UPR. We also discuss the possible involvement of ER stress in the pathogenesis of Alzheimer’s disease (AD). Potential therapeutic opportunities for diseases targeting ER stress is also described.

scholarly journals The translocon-associated protein (TRAP) complex regulates quality control of N-linked glycosylation during ER stress

2021 ◽  
Vol 7 (3) ◽  
pp. eabc6364
Author(s):  
Chatchai Phoomak ◽  
Wei Cui ◽  
Thomas J. Hayman ◽  
Seok-Ho Yu ◽  
Peng Zhao ◽  
...  
Keyword(s):  
Quality Control ◽  
Er Stress ◽  
Posttranslational Modification ◽  
Stress Protein ◽  
Transcriptional Signature ◽  
Protein Levels ◽  
Er Chaperone ◽  
Er Homeostasis ◽  
Glycoprotein Quality Control ◽  
Over Time

Asparagine (N)–linked glycosylation is required for endoplasmic reticulum (ER) homeostasis, but how this co- and posttranslational modification is maintained during ER stress is unknown. Here, we introduce a fluorescence-based strategy to detect aberrant N-glycosylation in individual cells and identify a regulatory role for the heterotetrameric translocon-associated protein (TRAP) complex. Unexpectedly, cells with knockout of SSR3 or SSR4 subunits restore N-glycosylation over time concurrent with a diminished ER stress transcriptional signature. Activation of ER stress or silencing of the ER chaperone BiP exacerbates or rescues the glycosylation defects, respectively, indicating that SSR3 and SSR4 enable N-glycosylation during ER stress. Protein levels of the SSR3 subunit are ER stress and UBE2J1 dependent, revealing a mechanism that coordinates upstream N-glycosylation proficiency with downstream ER-associated degradation and proteostasis. The fidelity of N-glycosylation is not static in both nontransformed and tumor cells, and the TRAP complex regulates ER glycoprotein quality control under conditions of stress.

scholarly journals A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Madlen Stephani ◽  
Lorenzo Picchianti ◽  
Alexander Gajic ◽  
Rebecca Beveridge ◽  
Emilio Skarwan ◽  
...  
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Mammalian Cells ◽  
Control Mechanisms ◽  
Receptor Complex ◽  
Er Quality Control ◽  
Proteotoxic Stress ◽  
Quality Control Mechanism ◽  
Passenger Proteins

Eukaryotes have evolved various quality control mechanisms to promote proteostasis in the endoplasmic reticulum (ER). Selective removal of certain ER domains via autophagy (termed as ER-phagy) has emerged as a major quality control mechanism. However, the degree to which ER-phagy is employed by other branches of ER-quality control remains largely elusive. Here, we identify a cytosolic protein, C53, that is specifically recruited to autophagosomes during ER-stress, in both plant and mammalian cells. C53 interacts with ATG8 via a distinct binding epitope, featuring a shuffled ATG8 interacting motif (sAIM). C53 senses proteotoxic stress in the ER lumen by forming a tripartite receptor complex with the ER-associated ufmylation ligase UFL1 and its membrane adaptor DDRGK1. The C53/UFL1/DDRGK1 receptor complex is activated by stalled ribosomes and induces the degradation of internal or passenger proteins in the ER. Consistently, the C53 receptor complex and ufmylation mutants are highly susceptible to ER stress. Thus, C53 forms an ancient quality control pathway that bridges selective autophagy with ribosome-associated quality control in the ER.

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