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Clinics in Liver Disease Nov 2009The endoplasmic reticulum (ER) is the key cellular organelle involved in protein homoeostasis. The unfolded protein response (UPR) is a fundamental cellular process... (Review)
Review
The endoplasmic reticulum (ER) is the key cellular organelle involved in protein homoeostasis. The unfolded protein response (UPR) is a fundamental cellular process triggered by ER stress because of lack of ATP or primary ER dysfunction. The UPR is activated and dysregulated in non-alcoholic fatty liver disease (NAFLD). The UPR has been shown to be involved in both normal physiologic functions and the cellular response to a host of pathologic states. This article reviews the pathways by which the UPR unfolds and its potential role in the development and progression of NAFLD.
Topics: Animals; Apoptosis; Endoplasmic Reticulum; Fatty Liver; Humans; Protein Folding; Unfolded Protein Response
PubMed: 19818306
DOI: 10.1016/j.cld.2009.07.004 -
Trends in Endocrinology and Metabolism:... May 2009The endoplasmic reticulum (ER) is a metabolic organelle and an ideal nutrient sensor. In response to hypoglycemia, hyperglycemia or fatty acid overload, the ER triggers... (Review)
Review
The endoplasmic reticulum (ER) is a metabolic organelle and an ideal nutrient sensor. In response to hypoglycemia, hyperglycemia or fatty acid overload, the ER triggers the unfolded protein response, which represses protein synthesis, alters insulin responsiveness and favors apoptosis. In addition, the ER affects steroid hormone activation and autophagy. The primary aim of these responses is to adjust the metabolism to environmental changes. Failure of the ER to adapt to changes in nutrient availability can result in a pathological transition in ER functions, as observed in cases of obesity-related diseases. This review highlights the recent evidence that the ER has a prominent role in cellular adaptation, as well as in the pathomechanism of type 2 diabetes.
Topics: Amino Acids; Animals; Cholesterol; Endoplasmic Reticulum; Humans; Insulin; Pyrimidine Nucleotides; Signal Transduction; Triglycerides
PubMed: 19349192
DOI: 10.1016/j.tem.2009.01.003 -
Wiley Interdisciplinary Reviews. RNA 2014Almost all cells use mRNA localization to establish spatial control of protein synthesis. One of the best-studied examples is the targeting and anchoring of mRNAs... (Review)
Review
Almost all cells use mRNA localization to establish spatial control of protein synthesis. One of the best-studied examples is the targeting and anchoring of mRNAs encoding secreted, organellar, and membrane-bound proteins to the surface of the endoplasmic reticulum (ER). In this review, we provide a historical perspective on the research that elucidated the canonical protein-mediated targeting of nascent-chain ribosome mRNA complexes to the surface of the ER. We then discuss subsequent studies which provided concrete evidence that a subpopulation of mRNAs utilize a translation-independent mechanism to localize to the surface of this organelle. This alternative mechanism operates alongside the signal recognition particle (SRP) mediated co-translational targeting pathway to promote proper mRNA localization to the ER. Recent work has uncovered trans-acting factors, such as the mRNA receptor p180, and cis-acting elements, such as transmembrane domain coding regions, that are responsible for this alternative mRNA localization process. Furthermore, some unanticipated observations have raised the possibility that this alternative pathway may be conserved from bacteria to mammalian cells.
Topics: Endoplasmic Reticulum; RNA, Messenger
PubMed: 24644132
DOI: 10.1002/wrna.1225 -
Cell Calcium 2005The endoplasmic reticulum (ER) is a subcellular compartment playing a central role in calcium storage and signaling. Disturbances of ER calcium homeostasis constitute a... (Review)
Review
The endoplasmic reticulum (ER) is a subcellular compartment playing a central role in calcium storage and signaling. Disturbances of ER calcium homeostasis constitute a severe form of stress interfering with central functions of this structure including the folding and processing of newly synthesized membrane and secretory proteins. Blocking the folding and processing reactions results in the accumulation of unfolded proteins forming potentially toxic aggregates. To restore ER functioning, specific stress responses are activated one of which is the unfolded protein response (UPR). UPR is characterized by a shutdown of global protein synthesis and activation of expression of genes coding for ER-resident proteins that are involved in the folding and processing reactions. ER calcium homeostasis is therefore inevitably associated with major cellular functions, including gene transcription and translation. ER calcium homeostasis und ER functions are believed to be impaired in various degenerative diseases of the brain including Alzheimer's, Parkinson's and Huntington's disease, and amyotrophic lateral sclerosis. ER functioning has also been shown to be disturbed in acute pathological states of the brain such as ischemia and trauma, which have been identified as risk factors for the development of degenerative diseases. This implies that there are common underlying pathomechanisms. This review will summarize new observations suggesting that impairment of ER functioning may be a common denominator of pathological processes resulting in neuronal cell injury in acute disorders and degenerative diseases of the brain.
Topics: Animals; Brain; Endoplasmic Reticulum; Humans; Neurodegenerative Diseases; Oxidative Stress
PubMed: 16087231
DOI: 10.1016/j.ceca.2005.06.019 -
Life Sciences Oct 2017Understanding the mechanism of nanoparticle (NP) induced toxicity is important for nanotoxicological and nanomedicinal studies. Endoplasmic reticulum (ER) is a crucial... (Review)
Review
Understanding the mechanism of nanoparticle (NP) induced toxicity is important for nanotoxicological and nanomedicinal studies. Endoplasmic reticulum (ER) is a crucial organelle involved in proper protein folding. High levels of misfolded proteins in the ER could lead to a condition termed as ER stress, which may ultimately influence the fate of cells and development of human diseases. In this review, we summarized studies about effects of NP exposure on ER stress. A variety of NPs, especially metal-based NPs, could induce morphological changes of ER and activate ER stress pathway both in vivo and in vitro. In addition, modulation of ER stress by chemicals has been shown to alter the toxicity of NPs. These studies in combination suggested that ER stress could be the mechanism responsible for NP induced toxicity. Meanwhile, nanomedicinal studies also used ER stress inducing NPs or NPs loaded with ER stress inducer to selectively induce ER stress mediated apoptosis in cancer cells for cancer therapy. In contrast, alleviation of ER stress by NPs has also been shown as a strategy to cure metabolic diseases. In conclusion, exposure to NPs may modulate ER stress, which could be a target for future nanotoxicological and nanomedicinal studies.
Topics: Animals; Apoptosis; Cell Line, Tumor; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Humans; Nanomedicine; Nanoparticles; Particle Size; Protein Folding
PubMed: 28782531
DOI: 10.1016/j.lfs.2017.08.003 -
Acta Biochimica Polonica 2005The ER is one of the most important folding compartments within the cell, as well as an intracellular Ca(2+) storage organelle and it contains a number of Ca(2+)... (Review)
Review
The ER is one of the most important folding compartments within the cell, as well as an intracellular Ca(2+) storage organelle and it contains a number of Ca(2+) regulated molecular chaperones responsible for the proper folding of glycosylated as well as non-glycosylated proteins. The luminal environment of the ER contains Ca(2+) which is involved in regulating chaperones such as calnexin and calreticulin, as well as apoptotic proteins caspase-12 and Bap31, which may play an important role in determining cellular sensitivity to ER stress and apoptosis. The ER quality control system consists of several molecular chaperones, including calnexin, that assist in properly folding proteins and transporting them through the ER as well as sensing misfolded proteins, attempting to refold them and if this is not possible, targeting them for degradation. Accumulation of misfolded protein in the ER leads to activation of genes responsible for the expression of ER chaperones. The UPR mechanism involves transcriptional activation of chaperones by the membrane-localized transcription factor ATF6, in conjunction with the ER membrane kinase IRE1, as well as translational repression of protein synthesis by another ER membrane kinase PERK. When accumulation of misfolded protein becomes toxic, apoptosis is triggered, potentially with IRE1 involved in signaling via caspase-12. Both the extrinsic and intrinsic apoptotic pathways appear to culminate in the activation of caspases and this results in the recruitment of mitochondria in an essential amplifying manner. Bap31 may direct pro-apoptotic crosstalk between the ER and the mitochondria via Ca(2+) in conjunction with caspase-12 and calnexin. Accordingly, ER stress and the resultant Ca(2+) release must be very carefully regulated because of their effects in virtually all areas of cell function.
Topics: Animals; Apoptosis; Endoplasmic Reticulum; Humans; Models, Biological; Molecular Chaperones
PubMed: 15933766
DOI: No ID Found -
The FEBS Journal Jan 2019Endoplasmic reticulum (ER) stress is a mechanism that allows the protection of normal cellular functions in response to both internal perturbations, such as accumulation... (Review)
Review
Endoplasmic reticulum (ER) stress is a mechanism that allows the protection of normal cellular functions in response to both internal perturbations, such as accumulation of unfolded proteins, and external perturbations, for example redox stress, UVB irradiation, and infection. A hallmark of ER stress is the accumulation of misfolded and unfolded proteins. Physiological levels of ER stress trigger the unfolded protein response (UPR) that is required to restore normal ER functions. However, the UPR can also initiate a cell death program/apoptosis pathway in response to excessive or persistent ER stress. Recently, it has become evident that chronic ER stress occurs in several diseases, including skin diseases such as Darier's disease, rosacea, vitiligo and melanoma; furthermore, it is suggested that ER stress is directly involved in the pathogenesis of these disorders. Here, we review the role of ER stress in skin function, and discuss its significance in skin diseases.
Topics: Animals; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Humans; Protein Folding; Signal Transduction; Skin; Skin Diseases; Unfolded Protein Response
PubMed: 30586218
DOI: 10.1111/febs.14739 -
Developmental Cell Apr 2021The endoplasmic reticulum (ER) is a ubiquitous organelle that is vital to the life of eukaryotic cells. It synthesizes essential lipids and proteins and initiates the... (Review)
Review
The endoplasmic reticulum (ER) is a ubiquitous organelle that is vital to the life of eukaryotic cells. It synthesizes essential lipids and proteins and initiates the glycosylation of intracellular and surface proteins. As such, the ER is necessary for cell growth and communication with the external environment. The ER is also a highly dynamic organelle, whose structure is continuously remodeled through an interaction with the cytoskeleton and the action of specialized ER shapers. Recent and significant advances in ER studies have brought to light conserved and unique features underlying the structure and function of this organelle in plant cells. In this review, exciting developments in the understanding of the mechanisms for plant ER structural and functional homeostasis, particularly those that underpin ER network architecture and ER degradation, are presented and discussed.
Topics: Cytoskeleton; Endoplasmic Reticulum; Homeostasis; Plants
PubMed: 33662257
DOI: 10.1016/j.devcel.2021.02.008 -
Circulation Research May 2023
Topics: Mitochondria; Endoplasmic Reticulum; Heart; Endoplasmic Reticulum Stress; Apoptosis
PubMed: 37228240
DOI: 10.1161/CIRCRESAHA.123.322911 -
Progress in Molecular and Subcellular... 2021Calreticulin is well known as an ER-resident protein that serves as the major endoplasmic reticulum (ER) Ca binding protein. This protein has been the major topic of...
Calreticulin is well known as an ER-resident protein that serves as the major endoplasmic reticulum (ER) Ca binding protein. This protein has been the major topic of discussion in an international workshop that has been meeting for a quarter of a century. In sharing information about this protein, the field also witnessed remarkable insights into the importance of the ER as an organelle and the role of ER Ca in coordinating ER and cellular functions. Recent technological advances have helped to uncover the contributions of calreticulin in maintaining Ca homeostasis in the ER and to unravel its involvement in a multitude of cellular processes as highlighted in this collection of articles. The continuing revelations of unexpected involvement of calreticulin and Ca in many critical aspects of cellular function promises to further improve insights into the significance of this protein in the promotion of physiology as well as prevention of pathology.
Topics: Calreticulin; Endoplasmic Reticulum; Homeostasis; Lens, Crystalline
PubMed: 34050859
DOI: 10.1007/978-3-030-67696-4_1