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 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 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 Crucial Players for Inter-Organelle Communication: PI5P4Ks and Their Lipid Product PI-4,5-P2 Come to the Surface

2022 ◽  
Vol 9 ◽  
Author(s):  
Archna Ravi ◽  
Lavinia Palamiuc ◽  
Brooke M. Emerling
Keyword(s):  
Stress Response ◽  
Human Diseases ◽  
Type Ii ◽  
Metabolic Homeostasis ◽  
Cellular Homeostasis ◽  
Evolutionarily Conserved ◽  
Lipid Product ◽  
Canonical Type ◽  
Organelle Communication ◽  
A Minor

While organelles are individual compartments with specialized functions, it is becoming clear that organellar communication is essential for maintaining cellular homeostasis. This cooperation is carried out by various interactions taking place on the membranes of organelles. The membranes themselves contain a multitude of proteins and lipids that mediate these connections and one such class of molecules facilitating these relations are the phospholipids. There are several phospholipids, but the focus of this perspective is on a minor group called the phosphoinositides and specifically, phosphatidylinositol 4,5-bisphosphate (PI-4,5-P2). This phosphoinositide, on intracellular membranes, is largely generated by the non-canonical Type II PIPKs, namely, Phosphotidylinositol-5-phosphate-4-kinases (PI5P4Ks). These evolutionarily conserved enzymes are emerging as key stress response players in cells. Further, PI5P4Ks have been shown to modulate pathways by regulating organelle crosstalk, revealing roles in preserving metabolic homeostasis. Here we will attempt to summarize the functions of the PI5P4Ks and their product PI-4,5-P2 in facilitating inter-organelle communication and how they impact cellular health as well as their relevance to human diseases.

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.

scholarly journals A molecular pore spans the double membrane of the coronavirus replication organelle

Science ◽  
2020 ◽  
Vol 369 (6509) ◽  
pp. 1395-1398 ◽  
Author(s):  
Georg Wolff ◽  
Ronald W. A. L. Limpens ◽  
Jessika C. Zevenhoven-Dobbe ◽  
Ulrike Laugks ◽  
Shawn Zheng ◽  
...  
Keyword(s):  
Drug Target ◽  
Rna Synthesis ◽  
Transmembrane Protein ◽  
Membrane Vesicle ◽  
Membrane Vesicles ◽  
Genome Replication ◽  
Messenger Rnas ◽  
Double Membrane ◽  
The Core ◽  
Cryo Electron Microscopy

Coronavirus genome replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored microenvironment for viral RNA synthesis in the infected cell. However, it is unclear how newly synthesized genomes and messenger RNAs can travel from these sealed replication compartments to the cytosol to ensure their translation and the assembly of progeny virions. In this study, we used cellular cryo–electron microscopy to visualize a molecular pore complex that spans both membranes of the double-membrane vesicle and would allow export of RNA to the cytosol. A hexameric assembly of a large viral transmembrane protein was found to form the core of the crown-shaped complex. This coronavirus-specific structure likely plays a key role in coronavirus replication and thus constitutes a potential drug target.

scholarly journals Virus-induced double-membrane vesicles

2014 ◽  
Vol 17 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Emmanuelle Blanchard ◽  
Philippe Roingeard
Keyword(s):  
Membrane Vesicles ◽  
Double Membrane

scholarly journals Double-Membrane Vesicles as Platforms for Viral Replication

2020 ◽  
Vol 28 (12) ◽  
pp. 1022-1033 ◽  
Author(s):  
Georg Wolff ◽  
Charlotte E. Melia ◽  
Eric J. Snijder ◽  
Montserrat Bárcena
Keyword(s):  
Viral Replication ◽  
Membrane Vesicles ◽  
Double Membrane

scholarly journals The Porcine Deltacoronavirus Replication Organelle Comprises Double-Membrane Vesicles and Zippered Endoplasmic Reticulum with Double-Membrane Spherules

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1030 ◽  
Author(s):  
Nicole Doyle ◽  
Philippa C. Hawes ◽  
Jennifer Simpson ◽  
Lorin H. Adams ◽  
Helena J. Maier
Keyword(s):  
Endoplasmic Reticulum ◽  
Rna Synthesis ◽  
Membrane Vesicles ◽  
Viral Rna ◽  
Double Membrane ◽  
Severe Diarrhea ◽  
The Usa ◽  
History Of ◽  
Host Cell Interactions ◽  
Positive Strand Rna

Porcine deltacoronavirus (PDCoV) was first identified in Hong Kong in 2012 from samples taken from pigs in 2009. PDCoV was subsequently identified in the USA in 2014 in pigs with a history of severe diarrhea. The virus has now been detected in pigs in several countries around the world. Following the development of tissue culture adapted strains of PDCoV, it is now possible to address questions regarding virus–host cell interactions for this genera of coronavirus. Here, we presented a detailed study of PDCoV-induced replication organelles. All positive-strand RNA viruses induce the rearrangement of cellular membranes during virus replication to support viral RNA synthesis, forming the replication organelle. Replication organelles for the Alpha-, Beta-, and Gammacoronavirus genera have been characterized. All coronavirus genera induced the formation of double-membrane vesicles (DMVs). In addition, Alpha- and Betacoronaviruses induce the formation of convoluted membranes, while Gammacoronaviruses induce the formation of zippered endoplasmic reticulum (ER) with tethered double-membrane spherules. However, the structures induced by Deltacoronaviruses, particularly the presence of convoluted membranes or double-membrane spherules, are unknown. Initially, the dynamics of PDCoV strain OH-FD22 replication were assessed with the onset of viral RNA synthesis, protein synthesis, and progeny particle release determined. Subsequently, virus-induced membrane rearrangements were identified in infected cells by electron microscopy. As has been observed for all other coronaviruses studied to date, PDCoV replication was found to induce the formation of double-membrane vesicles. Significantly, however, PDCoV replication was also found to induce the formation of regions of zippered endoplasmic reticulum, small associated tethered vesicles, and double-membrane spherules. These structures strongly resemble the replication organelle induced by avian Gammacoronavirus infectious bronchitis virus.

Sign in / Sign up

Export Citation Format

Share Document