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Traffic (Copenhagen, Denmark) Sep 2022Endomembrane system compartments are significant elements in virtually all eukaryotic cells, supporting functions including protein synthesis, post-translational...
Endomembrane system compartments are significant elements in virtually all eukaryotic cells, supporting functions including protein synthesis, post-translational modifications and protein/lipid targeting. In terms of membrane area the endoplasmic reticulum (ER) is the largest intracellular organelle, but the origins of proteins defining the organelle and the nature of lineage-specific modifications remain poorly studied. To understand the evolution of factors mediating ER morphology and function we report a comparative genomics analysis of experimentally characterized ER-associated proteins involved in maintaining ER structure. We find that reticulons, REEPs, atlastins, Ufe1p, Use1p, Dsl1p, TBC1D20, Yip3p and VAPs are highly conserved, suggesting an origin at least as early as the last eukaryotic common ancestor (LECA), although many of these proteins possess additional non-ER functions in modern eukaryotes. Secondary losses are common in individual species and in certain lineages, for example lunapark is missing from the Stramenopiles and the Alveolata. Lineage-specific innovations include protrudin, Caspr1, Arl6IP1, p180, NogoR, kinectin and CLIMP-63, which are restricted to the Opisthokonta. Hence, much of the machinery required to build and maintain the ER predates the LECA, but alternative strategies for the maintenance and elaboration of ER shape and function are present in modern eukaryotes. Moreover, experimental investigations for ER maintenance factors in diverse eukaryotes are expected to uncover novel mechanisms.
Topics: Endoplasmic Reticulum; Eukaryotic Cells; Protein Transport
PubMed: 36040076
DOI: 10.1111/tra.12863 -
International Journal of Molecular... Apr 2024Dynamic regulation of the cellular proteome is mainly controlled in the endoplasmic reticulum (ER). Accumulation of misfolded proteins due to ER stress leads to the... (Review)
Review
Dynamic regulation of the cellular proteome is mainly controlled in the endoplasmic reticulum (ER). Accumulation of misfolded proteins due to ER stress leads to the activation of unfolded protein response (UPR). The primary role of UPR is to reduce the bulk of damages and try to drive back the system to the former or a new homeostatic state by autophagy, while an excessive level of stress results in apoptosis. It has already been proven that the proper order and characteristic features of both surviving and self-killing mechanisms are controlled by negative and positive feedback loops, respectively. The new results suggest that these feedback loops are found not only within but also between branches of the UPR, fine-tuning the response to ER stress. In this review, we summarize the recent knowledge of the dynamical characteristic of endoplasmic reticulum stress response mechanism by using both theoretical and molecular biological techniques. In addition, this review pays special attention to describing the mechanism of action of the dynamical features of the feedback loops controlling cellular life-and-death decision upon ER stress. Since ER stress appears in diseases that are common worldwide, a more detailed understanding of the behaviour of the stress response is of medical importance.
Topics: Animals; Humans; Apoptosis; Autophagy; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Unfolded Protein Response
PubMed: 38673953
DOI: 10.3390/ijms25084368 -
Cell Death & Disease Jul 2015Over the past few decades, understandings and evidences concerning the role of endoplasmic reticulum (ER) stress in deciding the cell fate have been constantly growing.... (Review)
Review
Over the past few decades, understandings and evidences concerning the role of endoplasmic reticulum (ER) stress in deciding the cell fate have been constantly growing. Generally, during ER stress, the signal transductions are mainly conducted by three ER stress transducers: protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring kinase 1 (IRE1) and activating transcription factor 6 (ATF6). Consequently, the harmful stimuli from the ER stress transducers induce apoptosis and autophagy, which share several crosstalks and eventually decide the cell fate. The dominance of apoptosis or autophagy induced by ER stress depends on the type and degree of the stimuli. When ER stress is too severe and prolonged, apoptosis is induced to eliminate the damaged cells; however, when stimuli are mild, cell survival is promoted to maintain normal physiological functions by inducing autophagy. Although all the three pathways participate in ER stress-induced apoptosis and autophagy, PERK shows several unique characteristics by interacting with some specific downstream effectors. Notably, there are some preliminary findings on PERK-dependent mechanisms switching autophagy and apoptosis. In this review, we particularly focused on the novel, intriguing and complicated role of PERK in ER stress-decided cell fate, and also discussed more roles of PERK in restoring cellular homeostasis. However, more in-depth knowledge of PERK in the future would facilitate our understanding about many human diseases and benefit in searching for new molecular therapeutic targets.
Topics: Animals; Apoptosis; Autophagy; Cell Differentiation; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Humans; eIF-2 Kinase
PubMed: 26225772
DOI: 10.1038/cddis.2015.183 -
Traffic (Copenhagen, Denmark) Apr 2016Production of a functional proteome is a major burden for our cells. Native proteins operate inside and outside the cells to eventually warrant life and adaptation to... (Review)
Review
Production of a functional proteome is a major burden for our cells. Native proteins operate inside and outside the cells to eventually warrant life and adaptation to metabolic and environmental changes, there is no doubt that production and inappropriate handling of misfolded proteins may cause severe disease states. This review focuses on protein destruction, which is, paradoxically, a crucial event for cell and organism survival. It regulates the physiological turnover of proteins and the clearance of faulty biosynthetic products. It mainly relies on the intervention of two catabolic machineries, the ubiquitin proteasome system and the (auto)lysosomal system. Here, we have selected five questions dealing with how, why and when proteins produced in the mammalian endoplasmic reticulum are eventually selected for destruction.
Topics: Animals; Endoplasmic Reticulum; Endoplasmic Reticulum-Associated Degradation; Humans; Proteolysis
PubMed: 27004930
DOI: 10.1111/tra.12373 -
Oncoimmunology 2022
Topics: Endoplasmic Reticulum; Endoplasmic Reticulum Chaperone BiP; Heat-Shock Proteins; Immunogenic Cell Death
PubMed: 35756845
DOI: 10.1080/2162402X.2022.2092328 -
American Journal of Physiology. Cell... Oct 2014
Topics: Animals; Disease; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Humans; Signal Transduction
PubMed: 24990648
DOI: 10.1152/ajpcell.00221.2014 -
Journal of Experimental Botany Mar 2020The availability of quantification methods for subcellular organelle dynamic analysis has increased rapidly over the last 20 years. The application of these techniques...
The availability of quantification methods for subcellular organelle dynamic analysis has increased rapidly over the last 20 years. The application of these techniques to contiguous subcellular structures that exhibit dynamic remodelling over a range of scales and orientations is challenging, as quantification of 'movement' rarely corresponds to traditional, qualitative classifications of types of organelle movement. The plant endoplasmic reticulum represents a particular challenge for dynamic quantification as it itself is an entirely contiguous organelle that is in a constant state of flux and gross remodelling, controlled by the actinomyosin cytoskeleton.
Topics: Biological Transport; Cytoskeleton; Endoplasmic Reticulum; Microtubules; Plants
PubMed: 31811712
DOI: 10.1093/jxb/erz543 -
Annual Review of Medicine 2012Perturbations in the normal functions of the endoplasmic reticulum (ER) trigger a signaling network that coordinates adaptive and apoptotic responses. There is... (Review)
Review
Perturbations in the normal functions of the endoplasmic reticulum (ER) trigger a signaling network that coordinates adaptive and apoptotic responses. There is accumulating evidence implicating prolonged ER stress in the development and progression of many diseases, including neurodegeneration, atherosclerosis, type 2 diabetes, liver disease, and cancer. With the improved understanding of the underlying molecular mechanisms, therapeutic interventions that target the ER stress response would be potential strategies to treat various diseases driven by prolonged ER stress.
Topics: Apoptosis; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Humans; Metabolic Diseases
PubMed: 22248326
DOI: 10.1146/annurev-med-043010-144749 -
Biochimica Et Biophysica Acta Oct 2014The endoplasmic reticulum (ER) is responsible for many housekeeping functions within the cell and is an important site for pathways that regulates its state of... (Review)
Review
The endoplasmic reticulum (ER) is responsible for many housekeeping functions within the cell and is an important site for pathways that regulates its state of homeostasis. When cellular states perturb ER functions, a phenomenon termed "ER stress" activates a number of pathways to counteract the associated damages; these pathways are together called the unfolded protein response (UPR). The UPR has a dualistic function; it exists to alleviate damage associated with ER stress, however, if this is not possible, then it signals for cell death through apoptosis. Cancer cells are shown to be very resilient under extreme environmental stress and an increasing number of studies have indicated that this may be largely due to an altered state of the UPR. The role of ER stress and the UPR in cancer is still not clear, however many components are involved and may prove to be promising targets in future anti-cancer therapy. This article is part of a Special Issue entitled: Calcium Signaling in Health and Disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau.
Topics: Animals; Cell Death; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Gene Expression Regulation, Neoplastic; Homeostasis; Humans; Neoplasm Proteins; Neoplasms; Signal Transduction; Unfolded Protein Response
PubMed: 24440276
DOI: 10.1016/j.bbamcr.2014.01.012 -
Molecular Dysfunctions of Mitochondria-Associated Endoplasmic Reticulum Contacts in Atherosclerosis.Oxidative Medicine and Cellular... 2021Atherosclerosis is a chronic lipid-driven inflammatory disease that results in the formation of lipid-rich and immune cell-rich plaques in the arterial wall, which has... (Review)
Review
Atherosclerosis is a chronic lipid-driven inflammatory disease that results in the formation of lipid-rich and immune cell-rich plaques in the arterial wall, which has high morbidity and mortality in the world. The mechanism of atherosclerosis is still unclear now. Potential hypotheses involved in atherosclerosis are chronic inflammation theory, lipid percolation theory, mononuclear-macrophage theory, endothelial cell (EC) injury theory, and smooth muscle cell (SMC) mutation theory. Changes of phospholipids, glucose, critical proteins, etc. on mitochondria-associated endoplasmic reticulum membrane (MAM) can cause the progress of atherosclerosis. This review describes the structural and functional interaction between mitochondria and endoplasmic reticulum (ER) and explains the role of critical molecules in the structure of MAM during atherosclerosis.
Topics: Atherosclerosis; Endoplasmic Reticulum; Humans; Mitochondria
PubMed: 34336087
DOI: 10.1155/2021/2424509