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Cells Sep 2019Efficiency and fidelity of protein secretion are achieved thanks to the presence of different steps, located sequentially in time and space along the secretory... (Review)
Review
Efficiency and fidelity of protein secretion are achieved thanks to the presence of different steps, located sequentially in time and space along the secretory compartment, controlling protein folding and maturation. After entering into the endoplasmic reticulum (ER), secretory proteins attain their native structure thanks to specific chaperones and enzymes. Only correctly folded molecules are allowed by quality control (QC) mechanisms to leave the ER and proceed to downstream compartments. Proteins that cannot fold properly are instead retained in the ER to be finally destined to proteasomal degradation. Exiting from the ER requires, in most cases, the use of coated vesicles, departing at the ER exit sites, which will fuse with the Golgi compartment, thus releasing their cargoes. Protein accumulation in the ER can be caused by a too stringent QC or by ineffective transport: these situations could be deleterious for the organism, due to the loss of the secreted protein, and to the cell itself, because of abnormal increase of protein concentration in the ER. In both cases, diseases can arise. In this review, we will describe the pathophysiology of protein folding and transport between the ER and the Golgi compartment.
Topics: Biological Transport; COP-Coated Vesicles; Endoplasmic Reticulum; Golgi Apparatus; Protein Folding; Protein Transport; Proteins
PubMed: 31500301
DOI: 10.3390/cells8091051 -
BioEssays : News and Reviews in... Feb 2021Autophagy functions in both selective and non-selective ways to maintain cellular homeostasis. Endoplasmic reticulum autophagy (ER-phagy) is a subclass of autophagy...
Autophagy functions in both selective and non-selective ways to maintain cellular homeostasis. Endoplasmic reticulum autophagy (ER-phagy) is a subclass of autophagy responsible for the degradation of the endoplasmic reticulum through selective encapsulation into autophagosomes. ER-phagy occurs both under physiological conditions and in response to stress cues, and plays a crucial role in maintaining the homeostatic control of the organelle. Although specific receptors that target parts of the ER membrane, as well as, internal proteins for lysosomal degradation have been identified, the molecular regulation of ER-phagy has been elusive. Recent work has uncovered novel regulators of ER-phagy that involve post-translational modifications of ER-resident proteins and functional cross-talk with other cellular processes. Herein, we discuss how morphology affects the function of the peripheral ER, and how ER-phagy modulates the turnover of this organelle. We also address how ER-phagy is regulated at the molecular level, considering implications relevant to human diseases.
Topics: Autophagy; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Humans; Membrane Proteins; Protein Processing, Post-Translational
PubMed: 33210303
DOI: 10.1002/bies.202000212 -
Journal of Plant Physiology Sep 2021Plant endoplasmic reticulum (ER) remodelling is likely to be important for its function in targeted protein secretion, organelle interaction and signal exchange. It has... (Review)
Review
Plant endoplasmic reticulum (ER) remodelling is likely to be important for its function in targeted protein secretion, organelle interaction and signal exchange. It has been known for decades that the structure and movement of the ER network is mainly regulated by the actin cytoskeleton through actin motor proteins and membrane-cytoskeleton adaptors. Recent discoveries also revealed alternative pathways that influence ER movement, through a microtubule-based machinery. Therefore, plants utilize both cytoskeletal components to drive ER dynamics, a process that is likely to be dependent on the cell type and the developmental stages. On the other hand, the ER membrane also has a direct effect towards the organization of the cytoskeletal network and disrupting the tethering factors at the ER-PM interface also rearranges the cytoskeletal structure. However, the influence of the ER network on the cytoskeleton organization has not been studied. In this review, we will provide an overview of the ER-cytoskeleton network in plants, and discuss the most recent discoveries in the field.
Topics: Cytoskeleton; Endoplasmic Reticulum; Plant Proteins; Plants
PubMed: 34298331
DOI: 10.1016/j.jplph.2021.153473 -
Current Opinion in Cell Biology Aug 2020Misfolded and mistargeted proteins in the early secretory pathway present significant risks to the cell. A diverse and integrated network of quality control pathways... (Review)
Review
Misfolded and mistargeted proteins in the early secretory pathway present significant risks to the cell. A diverse and integrated network of quality control pathways protects the cell from these threats. We focus on the discovery of new mechanisms that contribute to this protective network. Biochemical and structural advances in endoplasmic reticulum targeting fidelity, and in the redistribution of mistargeted substrates are discussed. We further review new discoveries in quality control at the inner nuclear membrane in the context of orphaned subunits. We consider developments in our understanding of cargo selection for endoplasmic reticulum export. Conflicting data on quality control by cargo receptor proteins are discussed and we look to important future questions for the field.
Topics: Endoplasmic Reticulum; Humans; Membrane Proteins; Models, Biological; Protein Folding; Secretory Pathway
PubMed: 32408120
DOI: 10.1016/j.ceb.2020.04.002 -
The FEBS Journal Jan 2019Various types of intracellular and extracellular stresses disturb homeostasis in the endoplasmic reticulum (ER) and, thus, trigger the ER stress response. Unavoidable... (Review)
Review
Various types of intracellular and extracellular stresses disturb homeostasis in the endoplasmic reticulum (ER) and, thus, trigger the ER stress response. Unavoidable and/or prolonged ER stress causes cell toxicity and occasionally cell death. The malfunction or death of irreplaceable cells leads to conformational diseases, including diabetes mellitus, ischemic diseases, metabolic diseases, and neurodegenerative diseases. In the past several decades, many studies have revealed the molecular mechanisms of the ER quality control system. Cells resolve ER stress by promptly and accurately reducing the amount of malfolded proteins. Recent reports have revealed that cells possess several types of ER-related disposal systems, including mRNA decay, proteasomal degradation, and autophagy. The removal of dispensable RNAs, proteins, and organelle parts may enable the effective maintenance of a functional ER. Here, we provide a comprehensive understanding of the ER quality control system by focusing on ER-related garbage disposal systems.
Topics: Animals; Autophagy; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Endoplasmic Reticulum-Associated Degradation; Humans; Proteasome Endopeptidase Complex; Protein Folding; Quality Control
PubMed: 29923316
DOI: 10.1111/febs.14589 -
The New Phytologist Apr 2020Secretory and transmembrane protein synthesis and initial modification are essential processes in protein maturation, and these processes are important for maintaining... (Review)
Review
Secretory and transmembrane protein synthesis and initial modification are essential processes in protein maturation, and these processes are important for maintaining protein homeostasis in the endoplasmic reticulum (ER). ER homeostasis can be disrupted by the accumulation of misfolded proteins, resulting in ER stress, due to specific intra- or extracellular stresses. Processes including the unfolded protein response (UPR), ER-associated degradation (ERAD) and autophagy are thought to play important roles in restoring ER homeostasis. Here, we focus on summarizing and analysing recent advances in our understanding of the role of ERAD in plant physiological processes, especially in plant adaption to biotic and abiotic stresses, and also identify several issues that still need to be resolved in this field.
Topics: Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Endoplasmic Reticulum-Associated Degradation; Plants; Unfolded Protein Response
PubMed: 31838748
DOI: 10.1111/nph.16369 -
DNA and Cell Biology Jun 2023The problems associated with economic development and social progress have led to an increase in the occurrence of cardiovascular diseases (CVDs), which affect the... (Review)
Review
The problems associated with economic development and social progress have led to an increase in the occurrence of cardiovascular diseases (CVDs), which affect the health of an increasing number of people and are a leading cause of disease and population mortality worldwide. Endoplasmic reticulum stress (ERS), a hot topic of interest for scholars in recent years, has been confirmed in numerous studies to be an important pathogenetic basis for many metabolic diseases and play an important role in maintaining physiological processes. The endoplasmic reticulum (ER) is a major organelle that is involved in protein folding and modification synthesis, and ERS occurs when several physiological and pathological factors allow excessive amounts of unfolded/misfolded proteins to accumulate. ERS often leads to initiation of the unfolded protein response (UPR) in a bid to re-establish tissue homeostasis; however, UPR has been documented to induce vascular remodeling and cardiomyocyte damage under various pathological conditions, leading to or accelerating the development of CVDs such as hypertension, atherosclerosis, and heart failure. In this review, we summarize the latest knowledge gained concerning ERS in terms of cardiovascular system pathophysiology, and discuss the feasibility of targeting ERS as a novel therapeutic target for the treatment of CVDs. Investigation of ERS has immense potential as a new direction for future research involving lifestyle intervention, the use of existing drugs, and the development of novel drugs that target and inhibit ERS.
Topics: Humans; Cardiovascular Diseases; Endoplasmic Reticulum Stress; Unfolded Protein Response; Endoplasmic Reticulum; Heart Failure
PubMed: 37140435
DOI: 10.1089/dna.2022.0532 -
Wiley Interdisciplinary Reviews. RNA 2023Cells are exposed to various pathological stimulus within the cardiovascular system that challenge cells to adapt and survive. Several of these pathological stimulus... (Review)
Review
Cells are exposed to various pathological stimulus within the cardiovascular system that challenge cells to adapt and survive. Several of these pathological stimulus alter the normal function of the endoplasmic reticulum (ER), leading to the accumulation of unfolded and misfolded proteins, thus triggering the unfolded protein response (UPR) to cope with the stress or trigger apoptosis of damaged cells. Downstream components of the UPR regulate transcription and translation reprogramming to ensure selective gene expression in response to pathological stimulus, including the expression of non-coding RNAs (ncRNAs). The ncRNAs play crucial roles in regulating transcription and translation, and their aberrant expression is associated with the development of cardiovascular disease (CVD). Notably, ncRNAs and ER stress can modulate each other and synergistically affect the development of CVD. Therefore, studying the interaction between ER stress and ncRNAs is necessary for effective prevention and treatment of CVD. In this review, we discuss the UPR signaling pathway and ncRNAs followed by the interplay regulation of ER stress and ncRNAs in CVD, which provides further insights into the understanding of the pathogenesis of CVD and therapeutic strategies. This article is categorized under: RNA in Disease and Development > RNA in Disease.
Topics: Humans; Cardiovascular Diseases; Endoplasmic Reticulum Stress; Unfolded Protein Response; Endoplasmic Reticulum; RNA, Untranslated
PubMed: 36420580
DOI: 10.1002/wrna.1767 -
The FEBS Journal Jan 2019The Endoplasmic Reticulum (ER) is the major site for secretory protein production in eukaryotic cells and like an efficient factory, it has the capacity to expand or... (Review)
Review
The Endoplasmic Reticulum (ER) is the major site for secretory protein production in eukaryotic cells and like an efficient factory, it has the capacity to expand or contract its output depending on the demand for its services. A primary function of the ER is to co-ordinate the quality control of proteins as they enter this folding factory at the base of the secretory pathway. Reduction-oxidation (redox) reactions have an important role to play in the quality control process, through the provision of disulphide bonds and by maintaining a favourable redox environment for oxidative protein folding. The ER is also a major contributor to calcium homeostasis and is a key site for lipid biosynthesis, two processes that additionally impact upon, and are influenced by, redox in the ER compartment.
Topics: Animals; Calcium; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Homeostasis; Humans; Oxidation-Reduction; Signal Transduction; Unfolded Protein Response
PubMed: 30062765
DOI: 10.1111/febs.14618 -
Biochemical Society Transactions Jun 2018The endoplasmic reticulum (ER) is the site of protein, lipid, phospholipid, steroid and oligosaccharide synthesis and modification, calcium ion storage, and... (Review)
Review
The endoplasmic reticulum (ER) is the site of protein, lipid, phospholipid, steroid and oligosaccharide synthesis and modification, calcium ion storage, and detoxification of endogenous and exogenous products. Its volume (and activity) must be maintained under normal growth conditions, must be expanded in a controlled manner on activation of ER stress programs and must be reduced to pre-stress size during the recovery phase that follows ER stress termination. ER-phagy is the constitutive or regulated fragmentation and delivery of ER fragments to lysosomal compartments for clearance. It gives essential contribution to the maintenance of cellular homeostasis, proteostasis, lipidostasis and oligosaccharidostasis (i.e. the capacity to produce the proteome, lipidome and oligosaccharidome in appropriate quality and quantity). ER turnover is activated on ER stress, nutrient deprivation, accumulation of misfolded polypeptides, pathogen attack and by activators of macroautophagy. The selectivity of these poorly characterized catabolic pathways is ensured by proteins displayed at the limiting membrane of the ER subdomain to be removed from cells. These proteins are defined as ER-phagy receptors and engage the cytosolic macroautophagy machinery via specific modules that associate with ubiquitin-like, cytosolic proteins of the Atg8/LC3/GABARAP family. In this review, we give an overview on selective ER turnover and on the yeast and mammalian ER-phagy receptors identified so far.
Topics: Animals; Autophagy; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Homeostasis
PubMed: 29802216
DOI: 10.1042/BST20170354