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Cells Jul 2020Contact sites between mitochondria and endoplasmic reticulum (ER) are points in which the two organelles are in close proximity. Due to their structural and functional... (Review)
Review
Contact sites between mitochondria and endoplasmic reticulum (ER) are points in which the two organelles are in close proximity. Due to their structural and functional complexity, their exploitation as pharmacological targets has never been considered so far. Notwithstanding, the number of compounds described to target proteins residing at these interfaces either directly or indirectly is rising. Here we provide original insight into mitochondria-ER contact sites (MERCs), with a comprehensive overview of the current MERCs pharmacology. Importantly, we discuss the considerable potential of MERCs to become a druggable target for the development of novel therapeutic strategies.
Topics: Animals; Endoplasmic Reticulum; Humans; Mitochondria; Mitochondrial Membranes
PubMed: 32646031
DOI: 10.3390/cells9071637 -
Experimental Cell Research Mar 2023Inflammatory bowel disease (IBD) is a chronic inflammatory disease involving the digestive tract, characterized by abdominal pain, diarrhea, rectal bleeding, and so on,... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic inflammatory disease involving the digestive tract, characterized by abdominal pain, diarrhea, rectal bleeding, and so on, which can make patients physically weakened and live difficultly. Although IBD has been recognized for many years, the pathogenesis of IBD has not yet been established and damage to intestinal barrier is thought to be closely associated with IBD. Intestinal barrier is an innate barrier that maintains the homeostasis of the intestinal environment and impedes pathogenic bacteria and toxins, and the endoplasmic reticulum (ER) has recently been found to be involved in maintaining the integrity of intestinal barrier. Endoplasmic reticulum stress (ERS) is a status of endoplasmic reticulum damaged when unfolded or misfolded proteins accumulate in excess of the degradation systematic clearance limit of the misfolded proteins. The regulation of ERS on protein folding synthesis and maintenance of cellular homeostasis is an important factor in influencing the integrity of the intestinal barrier. This paper mainly discusses the relationship between ERS and the intestinal barrier, aiming to understand the regulatory role of ERS on the intestinal barrier and the mechanism and to improve new solutions and notions for the treatment or prevention of IBD.
Topics: Humans; Endoplasmic Reticulum Stress; Intestines; Inflammatory Bowel Diseases; Protein Folding; Endoplasmic Reticulum; Intestinal Mucosa; Unfolded Protein Response
PubMed: 36634742
DOI: 10.1016/j.yexcr.2023.113472 -
Histochemistry and Cell Biology Feb 2021It has long been appreciated that the endoplasmic reticulum (ER) and mitochondria, organelles important for regular cell function and survival, also play key roles in... (Review)
Review
It has long been appreciated that the endoplasmic reticulum (ER) and mitochondria, organelles important for regular cell function and survival, also play key roles in pathogenesis of various lung diseases, including asthma, fibrosis, and infections. Alterations in processes regulated within these organelles, including but not limited to protein folding in the ER and oxidative phosphorylation in the mitochondria, are important in disease pathogenesis. In recent years it has also become increasingly apparent that organelle structure dictates function. It is now clear that organelles must maintain precise organization and localization for proper function. Newer microscopy capabilities have allowed the scientific community to reveal, via 3D imaging, that the structure of these organelles and their interactions with each other are a main component of regulating function and, therefore, effects on the disease state. In this review, we will examine how 3D imaging through techniques could allow advancements in knowledge of how the ER and mitochondria function and the roles they may play in lung epithelia in progression of lung disease.
Topics: Animals; Endoplasmic Reticulum; Epithelial Cells; Humans; Imaging, Three-Dimensional; Lung; Lung Diseases; Microscopy, Confocal; Microscopy, Electron; Mitochondria
PubMed: 33598824
DOI: 10.1007/s00418-020-01950-1 -
Cytoskeleton (Hoboken, N.J.) Jul 2020Eukaryotic membrane-bound organelles, exhibiting distinctive morphologies, dynamics and functions, are interconnected at membrane contact sites (MCSs) through numerous... (Review)
Review
Eukaryotic membrane-bound organelles, exhibiting distinctive morphologies, dynamics and functions, are interconnected at membrane contact sites (MCSs) through numerous tethering machineries. MCSs are required for many fundamental cellular processes, such as non-vesicular lipid transfer, calcium transport and organelle homeostasis. Actin cytoskeleton and myosin motors are known to dynamically interact with different membrane boundaries, facilitating organelle movements and partitioning. Intriguingly, recent studies have pinpointed a special participation of actomyosin at various MCSs involving the endoplasmic reticulum (ER), the most extensive membranous organelle in the cell. Here, I summarize emerging roles of ER MCSs in modulating actomyosin structures and discuss feedback functions of such actomyosin regulation at these MCSs.
Topics: Actomyosin; Cytoskeleton; Endoplasmic Reticulum; Humans
PubMed: 32543125
DOI: 10.1002/cm.21623 -
Cells & Development Jun 2022The development of the central nervous system requires a series of morphogenetic events that shape brain and spinal cord structures. Several brain regions and neural... (Review)
Review
The development of the central nervous system requires a series of morphogenetic events that shape brain and spinal cord structures. Several brain regions and neural circuits are formed by differential gene expression patterns and cell migration events involving neurons. During neurogenesis and neuritogenesis, increased demand for protein synthesis occurs to express key neuronal proteins to generate axons, dendrites, and synapsis. The endoplasmic reticulum (ER) is a central hub controlling protein homeostasis (proteostasis), impacting a wide range of cellular processes required for brain function. Although most of the field has focused on studying the role of ER stress in neurodegenerative diseases marked by abnormal protein aggregation, accumulating evidence indicates that ER proteostasis contributes to brain development and may impact neurodevelopmental processes such as neuronal migration, differentiation, and function. Here, we review emerging evidence linking neurodevelopment with ER proteostasis and its relevance to human disorders.
Topics: Brain; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Humans; Proteins; Proteostasis; Unfolded Protein Response
PubMed: 35483574
DOI: 10.1016/j.cdev.2022.203781 -
Molecular Cell Oct 2022Cellular quiescence-reversible exit from the cell cycle-is an important feature of many cell types important for organismal health. Quiescent cells activate protective... (Review)
Review
Cellular quiescence-reversible exit from the cell cycle-is an important feature of many cell types important for organismal health. Quiescent cells activate protective mechanisms that allow their persistence in the absence of growth and division for long periods of time. Aging and cellular dysfunction compromise the survival and re-activation of quiescent cells over time. Counteracting this decline are two interconnected organelles that lie at opposite ends of the secretory pathway: the endoplasmic reticulum and lysosomes. In this review, we highlight recent studies exploring the roles of these two organelles in quiescent cells from diverse contexts and speculate on potential other roles they may play, such as through organelle contact sites. Finally, we discuss emerging models of cellular quiescence, utilizing new cell culture systems and model organisms, that are suited to the mechanistic investigation of the functions of these organelles in quiescent cells.
Topics: Cell Cycle; Cell Division; Endoplasmic Reticulum; Homeostasis; Lysosomes
PubMed: 36044901
DOI: 10.1016/j.molcel.2022.08.005 -
The Journal of Cell Biology Jul 2024Bacteria, omnipresent in our environment and coexisting within our body, exert dual beneficial and pathogenic influences. These microorganisms engage in intricate... (Review)
Review
Bacteria, omnipresent in our environment and coexisting within our body, exert dual beneficial and pathogenic influences. These microorganisms engage in intricate interactions with the human body, impacting both human health and disease. Simultaneously, certain organelles within our cells share an evolutionary relationship with bacteria, particularly mitochondria, best known for their energy production role and their dynamic interaction with each other and other organelles. In recent years, communication between bacteria and mitochondria has emerged as a new mechanism for regulating the host's physiology and pathology. In this review, we delve into the dynamic communications between bacteria and host mitochondria, shedding light on their collaborative regulation of host immune response, metabolism, aging, and longevity. Additionally, we discuss bacterial interactions with other organelles, including chloroplasts, lysosomes, and the endoplasmic reticulum (ER).
Topics: Animals; Humans; Bacteria; Endoplasmic Reticulum; Host-Pathogen Interactions; Lysosomes; Mitochondria; Organelles
PubMed: 38748249
DOI: 10.1083/jcb.202310134 -
International Journal of Molecular... Mar 2021The revolutionary evolution in science and technology over the last few decades has made it possible to face more adequately three main challenges of modern medicine:... (Review)
Review
The revolutionary evolution in science and technology over the last few decades has made it possible to face more adequately three main challenges of modern medicine: changes in old diseases, the appearance of new diseases, and diseases that are unknown (mostly genetic), despite research efforts. In this paper we review the road travelled by pathologists in search of a method based upon the use of routine instruments and techniques which once were available for research only. The application to tissue studies of techniques from immunology, molecular biology, and genetics has allowed dynamic interpretations of biological phenomena with special regard to gene regulation and expression. That implies stepwise investigations, including light microscopy, immunohistochemistry, in situ hybridization, electron microscopy, molecular histopathology, protein crystallography, and gene sequencing, in order to progress from suggestive features detectable in routinely stained preparations to more characteristic, specific, and finally, pathognomonic features. Hematoxylin and Eosin (H&E)-stained preparations and appropriate immunohistochemical stains have enabled the recognition of phenotypic changes which may reflect genotypic alterations. That has been the case with hepatocytic inclusions detected in H&E-stained preparations, which appeared to correspond to secretory proteins that, due to genetic mutations, were retained within the rough endoplasmic reticulum (RER) and were deficient in plasma. The identification of this phenomenon affecting the molecules alpha-1-antitrypsin and fibrinogen has led to the discovery of a new field of cell organelle pathology, endoplasmic reticulum storage disease(s) (ERSD). Over fifty years, pathologists have wandered through a dark forest of complicated molecules with strange conformations, and by detailed observations in simple histopathological sections, accompanied by a growing background of molecular techniques and revelations, have been able to recognize and identify arrays of grotesque polypeptide arrangements.
Topics: Endoplasmic Reticulum; Gene Expression Regulation; Genotype; Humans; Immunohistochemistry; Metabolic Diseases; Mutation; alpha 1-Antitrypsin
PubMed: 33809321
DOI: 10.3390/ijms22062899 -
Journal of Microscopy Nov 2020The endoplasmic reticulum is a fascinating organelle at the core of the secretory pathway. It is responsible for the synthesis of one third of the cellular proteome and,... (Review)
Review
The endoplasmic reticulum is a fascinating organelle at the core of the secretory pathway. It is responsible for the synthesis of one third of the cellular proteome and, in plant cells, it produces receptors and transporters of hormones as well as the proteins responsible for the biosynthesis of critical components of a cellulosic cell wall. The endoplasmic reticulum structure resembles a spider-web network of interconnected tubules and cisternae that pervades the cell. The study of the dynamics and interaction of this organelles with other cellular structures such as the plasma membrane, the Golgi apparatus and the cytoskeleton, have been permitted by the implementation of fluorescent protein and advanced confocal imaging. In this review, we report on the findings that contributed towards the understanding of the endoplasmic reticulum morphology and function with the aid of fluorescent proteins, focusing on the contributions provided by pioneering work from the lab of the late Professor Chris Hawes.
Topics: Endoplasmic Reticulum; GTP Phosphohydrolases; Membrane Proteins; Organelles; Plant Cells; Plant Proteins
PubMed: 32426862
DOI: 10.1111/jmi.12909 -
The American Journal of Pathology Dec 2023Perturbations in lipid and protein homeostasis induce endoplasmic reticulum (ER) stress in metabolic dysfunction-associated steatotic liver disease (MASLD), formerly... (Review)
Review
Perturbations in lipid and protein homeostasis induce endoplasmic reticulum (ER) stress in metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease. Lipotoxic and proteotoxic stress can activate the unfolded protein response (UPR) transducers: inositol requiring enzyme1α, PKR-like ER kinase, and activating transcription factor 6α. Collectively, these pathways induce expression of genes that encode functions to resolve the protein folding defect and ER stress by increasing the protein folding capacity of the ER and degradation of misfolded proteins. The ER is also intimately connected with lipid metabolism, including de novo ceramide synthesis, phospholipid and cholesterol synthesis, and lipid droplet formation. Following their activation, the UPR transducers also regulate lipogenic pathways in the liver. With persistent ER stress, cellular adaptation fails, resulting in hepatocyte apoptosis, a pathological marker of liver disease. In addition to the ER-nucleus signaling activated by the UPR, the ER can interact with other organelles via membrane contact sites. Modulating intracellular communication between ER and endosomes, lipid droplets, and mitochondria to restore ER homeostasis could have therapeutic efficacy in ameliorating liver disease. Recent studies have also demonstrated that cells can convey ER stress by the release of extracellular vesicles. This review discusses lipotoxic ER stress and the central role of the ER in communicating ER stress to other intracellular organelles in MASLD pathogenesis.
Topics: Humans; Endoplasmic Reticulum Stress; Unfolded Protein Response; Non-alcoholic Fatty Liver Disease; Endoplasmic Reticulum
PubMed: 37689385
DOI: 10.1016/j.ajpath.2023.08.007