Special Issue "Proteostasis and Autophagy"

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Autophagy".

Deadline for manuscript submissions: closed (15 November 2018)

Special Issue Editors

Guest Editor
Prof. Dr. Christian Behl

Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
Website | E-Mail
Interests: proteostasis and autophagy; adaptation of neurons to cellular stress
Guest Editor
Dr. Andreas Kern

Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
Website | E-Mail
Interests: proteostasis and autophagy; the molecular function of RAB18 and RAB3GAP1

Special Issue Information

Dear Colleagues,

Proteins belong to the most skilled but unstable components of the cell and their correct folding, ensuring the correct three-dimensional structure, is the basis of their function. Misfolding of proteins during translation, or as a consequence of internal or external challenges, calls for refolding mechanisms. Finally, if refolding fails, the rapid degradation of the target protein is mandatory. Therefore, folding, refolding, and degradation are the pillars of protein homeostasis (proteostasis) that needs to be tightly controlled to maintain proper cellular functions. A great effort has been made to understand the regulators of proteostasis, which has resulted in the definition of a fine-tuned network of factors, including molecular chaperones and the two main protein degradation routes, the ubiquitin proteasome system and the autophagy-lysosomal pathways. Recently, it became evident that both degradation pathways are not working independently of each other, but that there is cross-talk between them. While proteasomal degradation is rather well-defined, data on autophagic degradation of proteins and also intracellular organelles are currently exploding, precisely because there are many links of changes in autophagy to diseases, including neurodegeneration. The maintenance of cellular proteostasis and, in particular, the adequate degradation and removal of dysfunctional proteins is of distinct importance for post-mitotic cells such as neurons.

This Special Issue aims to depict the recent role of autophagy in the maintenance of proteostasis and the particular importance of the degradative pathway in cellular conditions or disorders that are linked to increased appearance of misfolded and aggregated proteins. We look forward to your contributions.

Prof. Dr. Christian Behl
Dr. Andreas Kern
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • selective macroautophagy
  • proteostasis
  • protein misfolding / aggregation / degradation
  • disease

Published Papers (15 papers)

View options order results:
result details:
Displaying articles 1-15
Export citation of selected articles as:

Research

Jump to: Review

Open AccessFeature PaperArticle
ATG-18 and EPG-6 are Both Required for Autophagy but Differentially Contribute to Lifespan Control in Caenorhabditis elegans
Received: 31 January 2019 / Revised: 25 February 2019 / Accepted: 6 March 2019 / Published: 12 March 2019
PDF Full-text (4099 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
During macroautophagy, the human WIPI (WD-repeat protein interacting with phosphoinositides) proteins (WIPI1–4) function as phosphatidylinositol 3-phosphate effectors at the nascent autophagosome. Likewise, the two WIPI homologues in Caenorhabditis elegans, ATG-18 and EPG-6, play important roles in autophagy, whereby ATG-18 is considered to [...] Read more.
During macroautophagy, the human WIPI (WD-repeat protein interacting with phosphoinositides) proteins (WIPI1–4) function as phosphatidylinositol 3-phosphate effectors at the nascent autophagosome. Likewise, the two WIPI homologues in Caenorhabditis elegans, ATG-18 and EPG-6, play important roles in autophagy, whereby ATG-18 is considered to act upstream of EPG-6 at the onset of autophagy. Due to its essential role in autophagy, ATG-18 was found to be also essential for lifespan extension in Caenorhabditis elegans; however, this has not yet been addressed with regard to EPG-6. Here, we wished to address this point and generated mutant strains that expressed the autophagy marker GFP::LGG-1 (GFP-LC3 in mammals) and harbored functional deletions of either atg-18 (atg18(gk378)), epg-6 (epg-6(bp242)) or both (atg-18(gk378);epg-6(bp242)). Using quantitative fluorescence microscopy, Western blotting, and lifespan assessments, we provide evidence that in the absence of either ATG-18 or EPG-6 autophagy was impaired, and while atg-18 mutant animals showed a short-lived phenotype, lifespan was significantly increased in epg-6 mutant animals. We speculate that the long-lived phenotype of epg-6 mutant animals points towards an autophagy-independent function of EPG-6 in lifespan control that warrants further mechanistic investigations in future studies. Full article
(This article belongs to the Special Issue Proteostasis and Autophagy)
Figures

Figure 1

Open AccessArticle
Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo
Received: 29 January 2019 / Revised: 25 February 2019 / Accepted: 27 February 2019 / Published: 2 March 2019
PDF Full-text (2513 KB) | HTML Full-text | XML Full-text
Abstract
Dysfunction of autophagy and disturbed protein homeostasis are linked to the pathogenesis of human neurodegenerative diseases and the modulation of autophagy as the protein clearance process has become one key pharmacological target. Due to the role of sigma-1 receptors (Sig-1R) in learning and [...] Read more.
Dysfunction of autophagy and disturbed protein homeostasis are linked to the pathogenesis of human neurodegenerative diseases and the modulation of autophagy as the protein clearance process has become one key pharmacological target. Due to the role of sigma-1 receptors (Sig-1R) in learning and memory, and the described pleiotropic neuroprotective effects in various experimental paradigms, Sig-1R activation is recognized as one potential approach for prevention and therapy of neurodegeneration and, interestingly, in amyotrophic lateral sclerosis associated with mutated Sig-1R, autophagy is disturbed. Here we analyzed the effects of tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73), a muscarinic receptor ligand and Sig-1R agonist, on autophagy and proteostasis. We describe, at the molecular level, for the first time, that pharmacological Sig-1R activation a) enhances the autophagic flux in human cells and in Caenorhabditis elegans and b) increases proteostasis capacity, ultimately ameliorating paralysis caused by protein aggregation in C. elegans. ANAVEX2-73 is already in clinical investigation for the treatment of Alzheimer’s disease, and the novel activities of this compound on autophagy and proteostasis described here may have consequences for the use and further development of the Sig-1R as a drug target in the future. Moreover, our study defines the Sig-1R as an upstream modulator of canonical autophagy, which may have further implications for various conditions with dysfunctional autophagy, besides neurodegeneration. Full article
(This article belongs to the Special Issue Proteostasis and Autophagy)
Figures

Figure 1

Open AccessArticle
Control of the Epithelial-to-Mesenchymal Transition and Cancer Metastasis by Autophagy-Dependent SNAI1 Degradation
Received: 6 December 2018 / Revised: 31 January 2019 / Accepted: 5 February 2019 / Published: 6 February 2019
PDF Full-text (3147 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy, an intracellular degradation process, is essential for maintaining cell homeostasis by removing damaged organelles and proteins under various conditions of stress. In cancer, autophagy has conflicting functions. It plays a key role in protecting against cancerous transformation by maintaining genomic stability against [...] Read more.
Autophagy, an intracellular degradation process, is essential for maintaining cell homeostasis by removing damaged organelles and proteins under various conditions of stress. In cancer, autophagy has conflicting functions. It plays a key role in protecting against cancerous transformation by maintaining genomic stability against genotoxic components, leading to cancerous transformation. It can also promote cancer cell survival by supplying minimal amounts of nutrients during cancer progression. However, the molecular mechanisms underlying how autophagy regulates the epithelial-to-mesenchymal transition (EMT) and cancer metastasis are unknown. Here, we show that starvation-induced autophagy promotes Snail (SNAI1) degradation and inhibits EMT and metastasis in cancer cells. Interestingly, SNAI1 proteins were physically associated and colocalized with LC3 and SQSTM1 in cancer cells. We also found a significant decrease in the levels of EMT and metastatic proteins under starvation conditions. Furthermore, ATG7 knockdown inhibited autophagy-induced SNAI1 degradation in the cytoplasm, which was associated with a decrease in SNAI1 nuclear translocation. Moreover, cancer cell invasion and migration were significantly inhibited by starvation-induced autophagy. These findings suggest that autophagy-dependent SNAI1 degradation could specifically regulate EMT and cancer metastasis during tumorigenesis. Full article
(This article belongs to the Special Issue Proteostasis and Autophagy)
Figures

Graphical abstract

Open AccessArticle
Functional Characterization of Ubiquitin-Like Core Autophagy Protein ATG12 in Dictyostelium discoideum
Received: 7 December 2018 / Revised: 15 January 2019 / Accepted: 17 January 2019 / Published: 19 January 2019
Cited by 1 | PDF Full-text (7912 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Autophagy is a highly conserved intracellular degradative pathway that is crucial for cellular homeostasis. During autophagy, the core autophagy protein ATG12 plays, together with ATG5 and ATG16, an essential role in the expansion of the autophagosomal membrane. In this study we analyzed gene [...] Read more.
Autophagy is a highly conserved intracellular degradative pathway that is crucial for cellular homeostasis. During autophagy, the core autophagy protein ATG12 plays, together with ATG5 and ATG16, an essential role in the expansion of the autophagosomal membrane. In this study we analyzed gene replacement mutants of atg12 in Dictyostelium discoideum AX2 wild-type and ATG16‾ cells. RNAseq analysis revealed a strong enrichment of, firstly, autophagy genes among the up-regulated genes and, secondly, genes implicated in cell motility and phagocytosis among the down-regulated genes in the generated ATG12‾, ATG16‾ and ATG12‾/16‾ cells. The mutant strains showed similar defects in fruiting body formation, autolysosome maturation, and cellular viability, implying that ATG12 and ATG16 act as a functional unit in canonical autophagy. In contrast, ablation of ATG16 or of ATG12 and ATG16 resulted in slightly more severe defects in axenic growth, macropinocytosis, and protein homeostasis than ablation of only ATG12, suggesting that ATG16 fulfils an additional function in these processes. Phagocytosis of yeast, spore viability, and maximal cell density were much more affected in ATG12‾/16‾ cells, indicating that both proteins also have cellular functions independent of each other. In summary, we show that ATG12 and ATG16 fulfil autophagy-independent functions in addition to their role in canonical autophagy. Full article
(This article belongs to the Special Issue Proteostasis and Autophagy)
Figures

Figure 1

Open AccessCommunication
Possible Mechanisms by which Stefin B could Regulate Proteostasis and Oxidative Stress
Received: 8 November 2018 / Revised: 19 December 2018 / Accepted: 9 January 2019 / Published: 18 January 2019
PDF Full-text (1832 KB) | HTML Full-text | XML Full-text
Abstract
Human stefin B is a protease inhibitor from the family of cystatins. It was reported that it forms oligomers in cells. We have shown that it has a role in cell’s response to misfolded proteins. We also have shown that its oligomers bind [...] Read more.
Human stefin B is a protease inhibitor from the family of cystatins. It was reported that it forms oligomers in cells. We have shown that it has a role in cell’s response to misfolded proteins. We also have shown that its oligomers bind amyloid-beta (Aβ). Here, we discuss ways, how stefin B could reduce build-up of protein aggregates by other proteins and consequently reduces ROS and, how this might be connected to autophagy. When overexpressed, stefin B forms protein aggregates itself and these protein aggregates induce autophagy. Similarly, cystatin C was shown to bind Aβ and to induce autophagy. It is also suggested how more knowledge about the role of stefin B in a cell’s response to misfolded proteins could be used to modulate progressive myoclonus epilepsy of type 1 EPM1 disease. Full article
(This article belongs to the Special Issue Proteostasis and Autophagy)
Figures

Scheme 1

Review

Jump to: Research

Open AccessReview
Amyloid Beta and Phosphorylated Tau-Induced Defective Autophagy and Mitophagy in Alzheimer’s Disease
Received: 21 April 2019 / Revised: 10 May 2019 / Accepted: 21 May 2019 / Published: 22 May 2019
PDF Full-text (2038 KB) | HTML Full-text | XML Full-text
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory loss and multiple cognitive impairments. Several decades of intense research have revealed that multiple cellular changes are implicated in the development and progression of AD, including mitochondrial damage, synaptic dysfunction, amyloid beta [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory loss and multiple cognitive impairments. Several decades of intense research have revealed that multiple cellular changes are implicated in the development and progression of AD, including mitochondrial damage, synaptic dysfunction, amyloid beta (Aβ) formation and accumulation, hyperphosphorylated tau (P-Tau) formation and accumulation, deregulated microRNAs, synaptic damage, and neuronal loss in patients with AD. Among these, mitochondrial dysfunction and synaptic damage are early events in the disease process. Recent research also revealed that Aβ and P-Tau-induced defective autophagy and mitophagy are prominent events in AD pathogenesis. Age-dependent increased levels of Aβ and P-Tau reduced levels of several autophagy and mitophagy proteins. In addition, abnormal interactions between (1) Aβ and mitochondrial fission protein Drp1; (2) P-Tau and Drp1; and (3) Aβ and PINK1/parkin lead to an inability to clear damaged mitochondria and other cellular debris from neurons. These events occur selectively in affected AD neurons. The purpose of our article is to highlight recent developments of a Aβ and P-Tau-induced defective autophagy and mitophagy in AD. This article also summarizes several aspects of mitochondrial dysfunction, including abnormal mitochondrial dynamics (increased fission and reduced fusion), defective mitochondrial biogenesis, reduced ATP, increased free radicals and lipid peroxidation, and decreased cytochrome c oxidase (COX) activity and calcium dyshomeostasis in AD pathogenesis. Our article also discusses how reduced levels of Drp1, Aβ, and P-Tau can enhance the clearance of damaged mitochondria and other cellular debris by autophagy and mitophagy mechanisms. Full article
(This article belongs to the Special Issue Proteostasis and Autophagy)
Figures

Figure 1

Open AccessReview
The Role of Primary Cilia in the Crosstalk between the Ubiquitin–Proteasome System and Autophagy
Received: 29 December 2018 / Revised: 6 March 2019 / Accepted: 11 March 2019 / Published: 14 March 2019
PDF Full-text (1524 KB) | HTML Full-text | XML Full-text
Abstract
Protein degradation is a pivotal process for eukaryotic development and homeostasis. The majority of proteins are degraded by the ubiquitin–proteasome system and by autophagy. Recent studies describe a crosstalk between these two main eukaryotic degradation systems which allows for establishing a kind of [...] Read more.
Protein degradation is a pivotal process for eukaryotic development and homeostasis. The majority of proteins are degraded by the ubiquitin–proteasome system and by autophagy. Recent studies describe a crosstalk between these two main eukaryotic degradation systems which allows for establishing a kind of safety mechanism. If one of these degradation systems is hampered, the other compensates for this defect. The mechanism behind this crosstalk is poorly understood. Novel studies suggest that primary cilia, little cellular protrusions, are involved in the regulation of the crosstalk between the two degradation systems. In this review article, we summarise the current knowledge about the association between cilia, the ubiquitin–proteasome system and autophagy. Full article
(This article belongs to the Special Issue Proteostasis and Autophagy)
Figures

Figure 1

Open AccessFeature PaperReview
Presenilins and γ-Secretase in Membrane Proteostasis
Received: 1 February 2019 / Revised: 26 February 2019 / Accepted: 27 February 2019 / Published: 1 March 2019
Cited by 2 | PDF Full-text (953 KB) | HTML Full-text | XML Full-text
Abstract
The presenilin (PS) proteins exert a crucial role in the pathogenesis of Alzheimer disease (AD) by mediating the intramembranous cleavage of amyloid precursor protein (APP) and the generation of amyloid β-protein (Aβ). The two homologous proteins PS1 and PS2 represent the catalytic subunits [...] Read more.
The presenilin (PS) proteins exert a crucial role in the pathogenesis of Alzheimer disease (AD) by mediating the intramembranous cleavage of amyloid precursor protein (APP) and the generation of amyloid β-protein (Aβ). The two homologous proteins PS1 and PS2 represent the catalytic subunits of distinct γ-secretase complexes that mediate a variety of cellular processes, including membrane protein metabolism, signal transduction, and cell differentiation. While the intramembrane cleavage of select proteins by γ-secretase is critical in the regulation of intracellular signaling pathways, the plethora of identified protein substrates could also indicate an important role of these enzyme complexes in membrane protein homeostasis. In line with this notion, PS proteins and/or γ-secretase has also been implicated in autophagy, a fundamental process for the maintenance of cellular functions and homeostasis. Dysfunction in the clearance of proteins in the lysosome and during autophagy has been shown to contribute to neurodegeneration. This review summarizes the recent knowledge about the role of PS proteins and γ-secretase in membrane protein metabolism and trafficking, and the functional relation to lysosomal activity and autophagy. Full article
(This article belongs to the Special Issue Proteostasis and Autophagy)
Figures

Figure 1

Open AccessFeature PaperReview
Is Autophagy Involved in the Diverse Effects of Antidepressants?
Received: 15 December 2018 / Revised: 8 January 2019 / Accepted: 9 January 2019 / Published: 12 January 2019
Cited by 1 | PDF Full-text (268 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy has received increased attention as a conserved process governing cellular energy and protein homeostasis that is thus relevant in a range of physiological and pathophysiological conditions. Recently, autophagy has also been linked to depression, mainly through its involvement in the action of [...] Read more.
Autophagy has received increased attention as a conserved process governing cellular energy and protein homeostasis that is thus relevant in a range of physiological and pathophysiological conditions. Recently, autophagy has also been linked to depression, mainly through its involvement in the action of antidepressants. Some antidepressant drugs and psychotropic medication have been reported to exert beneficial effects in other diseases, for example, in cancer and neurodegenerative diseases. This review collates the evidence for the hypothesis that autophagy contributes to the effects of antidepressants beyond depression treatment. Full article
(This article belongs to the Special Issue Proteostasis and Autophagy)
Open AccessReview
The Roles of Ubiquitin-Binding Protein Shuttles in the Degradative Fate of Ubiquitinated Proteins in the Ubiquitin-Proteasome System and Autophagy
Received: 3 December 2018 / Revised: 24 December 2018 / Accepted: 3 January 2019 / Published: 10 January 2019
Cited by 2 | PDF Full-text (2091 KB) | HTML Full-text | XML Full-text
Abstract
The ubiquitin-proteasome system (UPS) and autophagy are the two major intracellular protein quality control (PQC) pathways that are responsible for cellular proteostasis (homeostasis of the proteome) by ensuring the timely degradation of misfolded, damaged, and unwanted proteins. Ubiquitination serves as the degradation signal [...] Read more.
The ubiquitin-proteasome system (UPS) and autophagy are the two major intracellular protein quality control (PQC) pathways that are responsible for cellular proteostasis (homeostasis of the proteome) by ensuring the timely degradation of misfolded, damaged, and unwanted proteins. Ubiquitination serves as the degradation signal in both these systems, but substrates are precisely targeted to one or the other pathway. Determining how and when cells target specific proteins to these two alternative PQC pathways and control the crosstalk between them are topics of considerable interest. The ubiquitin (Ub) recognition code based on the type of Ub-linked chains on substrate proteins was believed to play a pivotal role in this process, but an increasing body of evidence indicates that the PQC pathway choice is also made based on other criteria. These include the oligomeric state of the Ub-binding protein shuttles, their conformation, protein modifications, and the presence of motifs that interact with ATG8/LC3/GABARAP (autophagy-related protein 8/microtubule-associated protein 1A/1B-light chain 3/GABA type A receptor-associated protein) protein family members. In this review, we summarize the current knowledge regarding the Ub recognition code that is bound by Ub-binding proteasomal and autophagic receptors. We also discuss how cells can modify substrate fate by modulating the structure, conformation, and physical properties of these receptors to affect their shuttling between both degradation pathways. Full article
(This article belongs to the Special Issue Proteostasis and Autophagy)
Figures

Graphical abstract

Open AccessReview
Emerging Concepts and Functions of Autophagy as a Regulator of Synaptic Components and Plasticity
Received: 3 December 2018 / Revised: 23 December 2018 / Accepted: 3 January 2019 / Published: 9 January 2019
Cited by 2 | PDF Full-text (629 KB) | HTML Full-text | XML Full-text
Abstract
Protein homeostasis (proteostasis) is crucial to the maintenance of neuronal integrity and function. As the contact sites between neurons, synapses rely heavily on precisely regulated protein-protein interactions to support synaptic transmission and plasticity processes. Autophagy is an effective degradative pathway that can digest [...] Read more.
Protein homeostasis (proteostasis) is crucial to the maintenance of neuronal integrity and function. As the contact sites between neurons, synapses rely heavily on precisely regulated protein-protein interactions to support synaptic transmission and plasticity processes. Autophagy is an effective degradative pathway that can digest cellular components and maintain cellular proteostasis. Perturbations of autophagy have been implicated in aging and neurodegeneration due to a failure to remove damaged proteins and defective organelles. Recent evidence has demonstrated that autophagosome formation is prominent at synaptic terminals and neuronal autophagy is regulated in a compartment-specific fashion. Moreover, synaptic components including synaptic proteins and vesicles, postsynaptic receptors and synaptic mitochondria are known to be degraded by autophagy, thereby contributing to the remodeling of synapses. Indeed, emerging studies indicate that modulation of autophagy may be required for different forms of synaptic plasticity and memory formation. In this review, I will discuss our current understanding of the important role of neuronal/synaptic autophagy in maintaining neuronal function by degrading synaptic components and try to propose a conceptual framework of how the degradation of synaptic components via autophagy might impact synaptic function and contribute to synaptic plasticity. Full article
(This article belongs to the Special Issue Proteostasis and Autophagy)
Figures

Figure 1

Open AccessReview
The Autophagy-Lysosomal Pathways and Their Emerging Roles in Modulating Proteostasis in Tumors
Received: 15 November 2018 / Revised: 17 December 2018 / Accepted: 18 December 2018 / Published: 20 December 2018
Cited by 2 | PDF Full-text (1357 KB) | HTML Full-text | XML Full-text
Abstract
In normal physiological condition, the maintenance of cellular proteostasis is a prerequisite for cell growth, functioning, adapting to changing micro-environments, and responding to extracellular stress. Cellular proteostasis is maintained by specific proteostasis networks (PNs) to prevent protein misfolding, aggregating, and accumulating in subcellular [...] Read more.
In normal physiological condition, the maintenance of cellular proteostasis is a prerequisite for cell growth, functioning, adapting to changing micro-environments, and responding to extracellular stress. Cellular proteostasis is maintained by specific proteostasis networks (PNs) to prevent protein misfolding, aggregating, and accumulating in subcellular compartments. Commonly, the PNs are composed of protein synthesis, molecular chaperones, endoplasmic reticulum (ER), unfolded protein response (UPR), stress response pathways (SRPs), secretions, ubiquitin proteasome system (UPS), and autophagy-lysosomal pathways (ALPs). Although great efforts have been made to explore the underlying detailed mechanisms of proteostasis, there are many questions remain to explore, especially in proteostasis regulated by the ALPs. Proteostasis out-off-balance is correlated with various human diseases such as diabetes, stroke, inflammation, hypertension, pulmonary fibrosis, and Alzheimer’s disease. Enhanced regulation of PNs is observed in tumors, thereby indicating that proteostasis may play a pivotal role in tumorigenesis and cancer development. Recently, inhibitors targeting the UPS have shown to be failed in solid tumor treatment. However, there is growing evidence showing that the ALPs play important roles in regulation of proteostasis alone or with a crosstalk with other PNs in tumors. In this review, we provide insights into the proteostatic process and how it is regulated by the ALPs, such as macroautophagy, aggrephagy, chaperone-mediated autophagy, microautophagy, as well as mitophagy during tumor development. Full article
(This article belongs to the Special Issue Proteostasis and Autophagy)
Figures

Figure 1

Open AccessFeature PaperReview
The Role of ATG16 in Autophagy and The Ubiquitin Proteasome System
Received: 9 November 2018 / Revised: 17 December 2018 / Accepted: 18 December 2018 / Published: 20 December 2018
PDF Full-text (1808 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy and the ubiquitin proteasome system (UPS) are the two major cellular degradation pathways, which are critical for the maintenance of cell homeostasis. The two pathways differ in their mechanisms and clients. The evolutionary conserved ATG16 plays a key role in autophagy and [...] Read more.
Autophagy and the ubiquitin proteasome system (UPS) are the two major cellular degradation pathways, which are critical for the maintenance of cell homeostasis. The two pathways differ in their mechanisms and clients. The evolutionary conserved ATG16 plays a key role in autophagy and appears to link autophagy with the UPS. Here, we review the role of ATG16 in different species. We summarize the current knowledge of its functions in autophagosome membrane expansion and autophagosome formation, in Crohn’s disease, and in bacterial sequestration. In addition, we provide information on its autophagy-independent functions and its role in the crosstalk between autophagy and the UPS. Full article
(This article belongs to the Special Issue Proteostasis and Autophagy)
Figures

Figure 1

Open AccessReview
Role of Autophagy in Proteostasis: Friend and Foe in Cardiac Diseases
Cells 2018, 7(12), 279; https://doi.org/10.3390/cells7120279
Received: 20 November 2018 / Revised: 13 December 2018 / Accepted: 18 December 2018 / Published: 19 December 2018
Cited by 1 | PDF Full-text (1309 KB) | HTML Full-text | XML Full-text
Abstract
Due to ageing of the population, the incidence of cardiovascular diseases will increase in the coming years, constituting a substantial burden on health care systems. In particular, atrial fibrillation (AF) is approaching epidemic proportions. It has been identified that the derailment of proteostasis, [...] Read more.
Due to ageing of the population, the incidence of cardiovascular diseases will increase in the coming years, constituting a substantial burden on health care systems. In particular, atrial fibrillation (AF) is approaching epidemic proportions. It has been identified that the derailment of proteostasis, which is characterized by the loss of homeostasis in protein biosynthesis, folding, trafficking, and clearance by protein degradation systems such as autophagy, underlies the development of common cardiac diseases. Among various safeguards within the proteostasis system, autophagy is a vital cellular process that modulates clearance of misfolded and proteotoxic proteins from cardiomyocytes. On the other hand, excessive autophagy may result in derailment of proteostasis and therefore cardiac dysfunction. Here, we review the interplay between autophagy and proteostasis in the healthy heart, discuss the imbalance between autophagy and proteostasis during cardiac diseases, including AF, and finally explore new druggable targets which may limit cardiac disease initiation and progression. Full article
(This article belongs to the Special Issue Proteostasis and Autophagy)
Figures

Figure 1

Open AccessReview
Autophagy: An Essential Degradation Program for Cellular Homeostasis and Life
Cells 2018, 7(12), 278; https://doi.org/10.3390/cells7120278
Received: 2 December 2018 / Revised: 18 December 2018 / Accepted: 18 December 2018 / Published: 19 December 2018
Cited by 6 | PDF Full-text (2178 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy is a lysosome-dependent cellular degradation program that responds to a variety of environmental and cellular stresses. It is an evolutionarily well-conserved and essential pathway to maintain cellular homeostasis, therefore, dysfunction of autophagy is closely associated with a wide spectrum of human pathophysiological [...] Read more.
Autophagy is a lysosome-dependent cellular degradation program that responds to a variety of environmental and cellular stresses. It is an evolutionarily well-conserved and essential pathway to maintain cellular homeostasis, therefore, dysfunction of autophagy is closely associated with a wide spectrum of human pathophysiological conditions including cancers and neurodegenerative diseases. The discovery and characterization of the kingdom of autophagy proteins have uncovered the molecular basis of the autophagy process. In addition, recent advances on the various post-translational modifications of autophagy proteins have shed light on the multiple layers of autophagy regulatory mechanisms, and provide novel therapeutic targets for the treatment of the diseases. Full article
(This article belongs to the Special Issue Proteostasis and Autophagy)
Figures

Figure 1

Cells EISSN 2073-4409 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top