scholarly journals The Interplay of Reovirus with Autophagy

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Hung-Chuan Chiu ◽  
Sarah Richart ◽  
Fong-Yuan Lin ◽  
Wei-Li Hsu ◽  
Hung-Jen Liu
Keyword(s):  
Infectious Diseases ◽  
Membrane Vesicles ◽  
Protein Aggregates ◽  
Degradation Pathway ◽  
Cytoplasmic Protein ◽  
Cellular Homeostasis ◽  
Double Membrane ◽  
Protein Substrates ◽  
Reovirus Infection ◽  
Physiological Processes

Autophagy participates in multiple fundamental physiological processes, including survival, differentiation, development, and cellular homeostasis. It eliminates cytoplasmic protein aggregates and damaged organelles by triggering a series of events: sequestering the protein substrates into double-membrane vesicles, fusing the vesicles with lysosomes, and then degrading the autophagic contents. This degradation pathway is also involved in various disorders, for instance, cancers and infectious diseases. This paper provides an overview of modulation of autophagy in the course of reovirus infection and also the interplay of autophagy and reovirus.

scholarly journals Autophagy in Skin Diseases

Dermatology ◽  
2019 ◽  
Vol 235 (5) ◽  
pp. 380-389 ◽  
Author(s):  
Yeye Guo ◽  
Xu Zhang ◽  
Tianhao Wu ◽  
Xing Hu ◽  
Juan Su ◽  
...  
Keyword(s):  
Skin Diseases ◽  
Membrane Vesicles ◽  
Cellular Homeostasis ◽  
Double Membrane ◽  
Adaptive Process ◽  
Evolutionarily Conserved

Autophagy, or self-eating, is an evolutionarily conserved process in which cytosol and organelles are sequestered within double-membrane vesicles that deliver the contents to the lysosome/vacuole for the degradation and recycling of cytoplasmic components in eukaryotes. It is well recognized that autophagy plays an important role in maintaining cellular homeostasis under physiological and pathophysiological con­ditions and the upregulation of autophagy may serve as an adaptive process to provide nutrients and energy when under stresses. Recently, studies have illustrated that autophagy is intricately related to skin diseases. This review provides a brief synopsis of the process of autophagy and aims to elucidate the roles of autophagy in different skin diseases and to highlight the need for increased research in the field.

scholarly journals Therapeutic targeting of autophagy in neurodegenerative and infectious diseases

2015 ◽  
Vol 212 (7) ◽  
pp. 979-990 ◽  
Author(s):  
David C. Rubinsztein ◽  
Carla F. Bento ◽  
Vojo Deretic
Keyword(s):  
Infectious Diseases ◽  
Cell Survival ◽  
Membrane Vesicles ◽  
Supporting Cell ◽  
Human Biology ◽  
Infectious Agents ◽  
Therapeutic Targeting ◽  
Double Membrane ◽  
Pathogenic Agents ◽  
Cytoplasmic Aggregate

Autophagy is a conserved process that uses double-membrane vesicles to deliver cytoplasmic contents to lysosomes for degradation. Although autophagy may impact many facets of human biology and disease, in this review we focus on the ability of autophagy to protect against certain neurodegenerative and infectious diseases. Autophagy enhances the clearance of toxic, cytoplasmic, aggregate-prone proteins and infectious agents. The beneficial roles of autophagy can now be extended to supporting cell survival and regulating inflammation. Autophagic control of inflammation is one area where autophagy may have similar benefits for both infectious and neurodegenerative diseases beyond direct removal of the pathogenic agents. Preclinical data supporting the potential therapeutic utility of autophagy modulation in such conditions is accumulating.

scholarly journals Reticulophagy and Ribophagy: Regulated Degradation of Protein Production Factories

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Eduardo Cebollero ◽  
Fulvio Reggiori ◽  
Claudine Kraft
Keyword(s):  
Protein Production ◽  
Membrane Vesicles ◽  
Protein Aggregates ◽  
Nutrient Deprivation ◽  
Adaptation To Stress ◽  
Transport Pathway ◽  
Double Membrane ◽  
Selective Elimination ◽  
Long Time ◽  
Specific Degradation

During autophagy, cytosol, protein aggregates, and organelles are sequestered into double-membrane vesicles called autophagosomes and delivered to the lysosome/vacuole for breakdown and recycling of their basic components. In all eukaryotes this pathway is important for adaptation to stress conditions such as nutrient deprivation, as well as to regulate intracellular homeostasis by adjusting organelle number and clearing damaged structures. For a long time, starvation-induced autophagy has been viewed as a nonselective transport pathway; however, recent studies have revealed that autophagy is able to selectively engulf specific structures, ranging from proteins to entire organelles. In this paper, we discuss recent findings on the mechanisms and physiological implications of two selective types of autophagy: ribophagy, the specific degradation of ribosomes, and reticulophagy, the selective elimination of portions of the ER.

scholarly journals Autophagy: More Than a Nonselective Pathway

2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Fulvio Reggiori ◽  
Masaaki Komatsu ◽  
Kim Finley ◽  
Anne Simonsen
Keyword(s):  
Membrane Vesicles ◽  
Protein Aggregates ◽  
Catabolic Pathway ◽  
Transport Pathway ◽  
Double Membrane ◽  
Long Time ◽  
Specific Receptors ◽  
Aberrant Protein ◽  
The Impact

Autophagy is a catabolic pathway conserved among eukaryotes that allows cells to rapidly eliminate large unwanted structures such as aberrant protein aggregates, superfluous or damaged organelles, and invading pathogens. The hallmark of this transport pathway is the sequestration of the cargoes that have to be degraded in the lysosomes by double-membrane vesicles called autophagosomes. The key actors mediating the biogenesis of these carriers are the autophagy-related genes (ATGs). For a long time, it was assumed that autophagy is a bulk process. Recent studies, however, have highlighted the capacity of this pathway to exclusively eliminate specific structures and thus better fulfil the catabolic necessities of the cell. We are just starting to unveil the regulation and mechanism of these selective types of autophagy, but what it is already clearly emerging is that structures targeted to destruction are accurately enwrapped by autophagosomes through the action of specific receptors and adaptors. In this paper, we will briefly discuss the impact that the selective types of autophagy have had on our understanding of autophagy.

scholarly journals Autophagy regulation by acetylation—implications for neurodegenerative diseases

2021 ◽  
Vol 53 (1) ◽  
pp. 30-41
Author(s):  
Sung Min Son ◽  
So Jung Park ◽  
Marian Fernandez-Estevez ◽  
David C. Rubinsztein
Keyword(s):  
Neurodegenerative Diseases ◽  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Membrane Vesicles ◽  
Cell Types ◽  
Double Membrane ◽  
Physiological Processes ◽  
Evolutionarily Conserved ◽  
Development And Aging ◽  
Catabolic Process

AbstractPosttranslational modifications of proteins, such as acetylation, are essential for the regulation of diverse physiological processes, including metabolism, development and aging. Autophagy is an evolutionarily conserved catabolic process that involves the highly regulated sequestration of intracytoplasmic contents in double-membrane vesicles called autophagosomes, which are subsequently degraded after fusing with lysosomes. The roles and mechanisms of acetylation in autophagy control have emerged only in the last few years. In this review, we describe key molecular mechanisms by which previously identified acetyltransferases and deacetylases regulate autophagy. We highlight how p300 acetyltransferase controls mTORC1 activity to regulate autophagy under starvation and refeeding conditions in many cell types. Finally, we discuss how altered acetylation may impact various neurodegenerative diseases in which many of the causative proteins are autophagy substrates. These studies highlight some of the complexities that may need to be considered by anyone aiming to perturb acetylation under these conditions.

scholarly journals Factor XIII-A: An Indispensable “Factor” in Haemostasis and Wound Healing

2021 ◽  
Vol 22 (6) ◽  
pp. 3055
Author(s):  
Fahad S. M. Alshehri ◽  
Claire S. Whyte ◽  
Nicola J. Mutch
Keyword(s):  
Bone Marrow ◽  
Wound Healing ◽  
Crucial Role ◽  
Factor Xiii ◽  
Severe Bleeding ◽  
Bleeding Diathesis ◽  
Unknown Mechanism ◽  
Protein Substrates ◽  
Physiological Processes ◽  
Isopeptide Bonds

Factor XIII (FXIII) is a transglutaminase enzyme that catalyses the formation of ε-(γ-glutamyl)lysyl isopeptide bonds into protein substrates. The plasma form, FXIIIA2B2, has an established function in haemostasis, with fibrin being its principal substrate. A deficiency in FXIII manifests as a severe bleeding diathesis emphasising its crucial role in this pathway. The FXIII-A gene (F13A1) is expressed in cells of bone marrow and mesenchymal lineage. The cellular form, a homodimer of the A subunits denoted FXIII-A, was perceived to remain intracellular, due to the lack of a classical signal peptide for its release. It is now apparent that FXIII-A can be externalised from cells, by an as yet unknown mechanism. Thus, three pools of FXIII-A exist within the circulation: plasma where it circulates in complex with the inhibitory FXIII-B subunits, and the cellular form encased within platelets and monocytes/macrophages. The abundance of this transglutaminase in different forms and locations in the vasculature reflect the complex and crucial roles of this enzyme in physiological processes. Herein, we examine the significance of these pools of FXIII-A in different settings and the evidence to date to support their function in haemostasis and wound healing.

scholarly journals The ER Stress Surveillance (ERSU) pathway regulates daughter cell ER protein aggregate inheritance

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Francisco J Piña ◽  
Maho Niwa
Keyword(s):  
Cell Cycle ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Mother Cell ◽  
Daughter Cell ◽  
Protein Aggregates ◽  
Cytoplasmic Protein ◽  
Protein Aggregate ◽  
Daughter Cells ◽  
Simultaneous Visualization

Stress induced by cytoplasmic protein aggregates can have deleterious consequences for the cell, contributing to neurodegeneration and other diseases. Protein aggregates are also formed within the endoplasmic reticulum (ER), although the fate of ER protein aggregates, specifically during cell division, is not well understood. By simultaneous visualization of both the ER itself and ER protein aggregates, we found that ER protein aggregates that induce ER stress are retained in the mother cell by activation of the ER Stress Surveillance (ERSU) pathway, which prevents inheritance of stressed ER. In contrast, under conditions of normal ER inheritance, ER protein aggregates can enter the daughter cell. Thus, whereas cytoplasmic protein aggregates are retained in the mother cell to protect the functional capacity of daughter cells, the fate of ER protein aggregates is determined by whether or not they activate the ERSU pathway to impede transmission of the cortical ER during the cell cycle.

scholarly journals Myocardial Damage by SARS-CoV-2: Emerging Mechanisms and Therapies

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1880
Author(s):  
Huyen Tran Ho ◽  
Stefan Peischard ◽  
Nathalie Strutz-Seebohm ◽  
Karin Klingel ◽  
Guiscard Seebohm
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Energy Metabolism ◽  
Programmed Cell Death ◽  
Viral Replication ◽  
Ion Homeostasis ◽  
Membrane Vesicles ◽  
Cardiac Cells ◽  
The Body ◽  
Double Membrane

Evidence is emerging that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect various organs of the body, including cardiomyocytes and cardiac endothelial cells in the heart. This review focuses on the effects of SARS-CoV-2 in the heart after direct infection that can lead to myocarditis and an outline of potential treatment options. The main points are: (1) Viral entry: SARS-CoV-2 uses specific receptors and proteases for docking and priming in cardiac cells. Thus, different receptors or protease inhibitors might be effective in SARS-CoV-2-infected cardiac cells. (2) Viral replication: SARS-CoV-2 uses RNA-dependent RNA polymerase for replication. Drugs acting against ssRNA(+) viral replication for cardiac cells can be effective. (3) Autophagy and double-membrane vesicles: SARS-CoV-2 manipulates autophagy to inhibit viral clearance and promote SARS-CoV-2 replication by creating double-membrane vesicles as replication sites. (4) Immune response: Host immune response is manipulated to evade host cell attacks against SARS-CoV-2 and increased inflammation by dysregulating immune cells. Efficiency of immunosuppressive therapy must be elucidated. (5) Programmed cell death: SARS-CoV-2 inhibits programmed cell death in early stages and induces apoptosis, necroptosis, and pyroptosis in later stages. (6) Energy metabolism: SARS-CoV-2 infection leads to disturbed energy metabolism that in turn leads to a decrease in ATP production and ROS production. (7) Viroporins: SARS-CoV-2 creates viroporins that lead to an imbalance of ion homeostasis. This causes apoptosis, altered action potential, and arrhythmia.

scholarly journals The Origin, Dynamic Morphology, and PI4P-Independent Formation of Encephalomyocarditis Virus Replication Organelles

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
pp. e00420-18 ◽  
Author(s):  
C. E. Melia ◽  
H. M. van der Schaar ◽  
A. W. M. de Jong ◽  
H. R. Lyoo ◽  
E. J. Snijder ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Rna Synthesis ◽  
Electron Tomography ◽  
Membrane Vesicles ◽  
Encephalomyocarditis Virus ◽  
Escape Mutant ◽  
Membrane Structures ◽  
Double Membrane ◽  
Single Membrane ◽  
Phosphatidylinositol 4

ABSTRACTPicornaviruses induce dramatic rearrangements of endomembranes in the cells that they infect to produce dedicated platforms for viral replication. These structures, termed replication organelles (ROs), have been well characterized for theEnterovirusgenus of thePicornaviridae. However, it is unknown whether the diverse RO morphologies associated with enterovirus infection are conserved among other picornaviruses. Here, we use serial electron tomography at different stages of infection to assess the three-dimensional architecture of ROs induced by encephalomyocarditis virus (EMCV), a member of theCardiovirusgenus of the family of picornaviruses that is distantly related. Ultrastructural analyses revealed connections between early single-membrane EMCV ROs and the endoplasmic reticulum (ER), establishing the ER as a likely donor organelle for their formation. These early single-membrane ROs appear to transform into double-membrane vesicles (DMVs) as infection progresses. Both single- and double-membrane structures were found to support viral RNA synthesis, and progeny viruses accumulated in close proximity, suggesting a spatial association between RNA synthesis and virus assembly. Further, we explored the role of phosphatidylinositol 4-phosphate (PI4P), a critical host factor for both enterovirus and cardiovirus replication that has been recently found to expedite enterovirus RO formation rather than being strictly required. By exploiting an EMCV escape mutant, we found that low-PI4P conditions could also be overcome for the formation of cardiovirus ROs. Collectively, our data show that despite differences in the membrane source, there are striking similarities in the biogenesis, morphology, and transformation of cardiovirus and enterovirus ROs, which may well extend to other picornaviruses.IMPORTANCELike all positive-sense RNA viruses, picornaviruses induce the rearrangement of host cell membranes to form unique structures, or replication organelles (ROs), that support viral RNA synthesis. Here, we investigate the architecture and biogenesis of cardiovirus ROs and compare them with those induced by enteroviruses, members of the well-characterized picornavirus genusEnterovirus. The origins and dynamic morphologies of cardiovirus ROs are revealed using electron tomography, which points to the endoplasmic reticulum as the donor organelle usurped to produce single-membrane tubules and vesicles that transform into double-membrane vesicles. We show that PI4P, a critical lipid for cardiovirus and enterovirus replication, is not strictly required for the formation of cardiovirus ROs, as functional ROs with typical morphologies are formed under phosphatidylinositol 4-kinase type III alpha (PI4KA) inhibition in cells infected with an escape mutant. Our data show that the transformation from single-membrane structures to double-membrane vesicles is a conserved feature of cardiovirus and enterovirus infections that likely extends to other picornavirus genera.

scholarly journals Ultrastructural Evidence for Direct Renal Infection with SARS-CoV-2

2020 ◽  
Vol 31 (8) ◽  
pp. 1683-1687 ◽  
Author(s):  
Evan A. Farkash ◽  
Allecia M. Wilson ◽  
Jeffrey M. Jentzen
Keyword(s):  
Renal Failure ◽  
Light Microscopy ◽  
Virus Assembly ◽  
Light And Electron Microscopy ◽  
Membrane Vesicles ◽  
Renal Tissue ◽  
Double Membrane ◽  
Renal Tubular Epithelium ◽  
Renal Tubular ◽  
Renal Infection

BackgroundA significant fraction of patients with coronavirus disease 2019 (COVID-19) display abnormalities in renal function. Retrospective studies of patients hospitalized with COVID-19 in Wuhan, China, report an incidence of 3%–7% progressing to ARF, a marker of poor prognosis. The cause of the renal failure in COVID-19 is unknown, but one hypothesized mechanism is direct renal infection by the causative virus, SARS-CoV-2.MethodsWe performed an autopsy on a single patient who died of COVID-19 after open repair of an aortic dissection, complicated by hypoxic respiratory failure and oliguric renal failure. We used light and electron microscopy to examine renal tissue for evidence of SARS-CoV-2 within renal cells.ResultsLight microscopy of proximal tubules showed geographic isometric vacuolization, corresponding to a focus of tubules with abundant intracellular viral arrays. Individual viruses averaged 76 µm in diameter and had an envelope studded with crown-like, electron-dense spikes. Vacuoles contained double-membrane vesicles suggestive of partially assembled virus.ConclusionsThe presence of viral particles in the renal tubular epithelium that were morphologically identical to SARS-CoV-2, and with viral arrays and other features of virus assembly, provide evidence of a productive direct infection of the kidney by SARS-CoV-2. This finding offers confirmatory evidence that direct renal infection occurs in the setting of AKI in COVID-19. However, the frequency and clinical significance of direct infection in COVID-19 is unclear. Tubular isometric vacuolization observed with light microscopy, which correlates with double-membrane vesicles containing vacuoles observed with electronic microscopy, may be a useful histologic marker for active SARS-CoV-2 infection in kidney biopsy or autopsy specimens.

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