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  1. Article: Digest it all: the lysosomal turnover of cytoplasmic aggregates.

    Mauthe, Mario / Kampinga, Harm H / Hipp, Mark S / Reggiori, Fulvio

    Trends in biochemical sciences

    2022  Volume 48, Issue 3, Page(s) 216–228

    Abstract: Aggrephagy describes the selective lysosomal transport and turnover of cytoplasmic protein aggregates by macro-autophagy. In this process, protein aggregates and conglomerates are polyubiquitinated and then sequestered by autophagosomes. Soluble ... ...

    Abstract Aggrephagy describes the selective lysosomal transport and turnover of cytoplasmic protein aggregates by macro-autophagy. In this process, protein aggregates and conglomerates are polyubiquitinated and then sequestered by autophagosomes. Soluble selective autophagy receptors (SARs) are central to aggrephagy and physically bind to both ubiquitin and the autophagy machinery, thus linking the cargo to the forming autophagosomal membrane. Because the accumulation of protein aggregates is associated with cytotoxicity in several diseases, a better molecular understanding of aggrephagy might provide a conceptual framework to develop therapeutic strategies aimed at delaying the onset of these pathologies by preventing the buildup of potentially toxic aggregates. We review recent advances in our knowledge about the mechanism of aggrephagy.
    MeSH term(s) Sequestosome-1 Protein/metabolism ; Protein Aggregates ; Autophagy ; Autophagosomes ; Lysosomes/metabolism
    Chemical Substances Sequestosome-1 Protein ; Protein Aggregates
    Language English
    Publishing date 2022-10-21
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 194216-5
    ISSN 1362-4326 ; 0968-0004 ; 0376-5067
    ISSN (online) 1362-4326
    ISSN 0968-0004 ; 0376-5067
    DOI 10.1016/j.tibs.2022.09.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Hydroxychloroquine in rheumatic autoimmune disorders and beyond.

    Nirk, Eliise Laura / Reggiori, Fulvio / Mauthe, Mario

    EMBO molecular medicine

    2020  Volume 12, Issue 8, Page(s) e12476

    Abstract: Initially used as antimalarial drugs, hydroxychloroquine (HCQ) and, to a lesser extent, chloroquine (CQ) are currently being used to treat several diseases. Due to its cost-effectiveness, safety and efficacy, HCQ is especially used in rheumatic ... ...

    Abstract Initially used as antimalarial drugs, hydroxychloroquine (HCQ) and, to a lesser extent, chloroquine (CQ) are currently being used to treat several diseases. Due to its cost-effectiveness, safety and efficacy, HCQ is especially used in rheumatic autoimmune disorders (RADs), such as systemic lupus erythematosus, primary Sjögren's syndrome and rheumatoid arthritis. Despite this widespread use in the clinic, HCQ molecular modes of action are still not completely understood. By influencing several cellular pathways through different mechanisms, CQ and HCQ inhibit multiple endolysosomal functions, including autophagy, as well as endosomal Toll-like receptor activation and calcium signalling. These effects alter several aspects of the immune system with the synergistic consequence of reducing pro-inflammatory cytokine production and release, one of the most marked symptoms of RADs. Here, we review the current knowledge on the molecular modes of action of these drugs and the circumstances under which they trigger side effects. This is of particular importance as the therapeutic use of HCQ is expanding beyond the treatment of malaria and RADs.
    MeSH term(s) Arthritis, Rheumatoid/drug therapy ; Autoimmune Diseases/drug therapy ; Chloroquine ; Humans ; Hydroxychloroquine/therapeutic use ; Lupus Erythematosus, Systemic
    Chemical Substances Hydroxychloroquine (4QWG6N8QKH) ; Chloroquine (886U3H6UFF)
    Keywords covid19
    Language English
    Publishing date 2020-07-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2467145-9
    ISSN 1757-4684 ; 1757-4676
    ISSN (online) 1757-4684
    ISSN 1757-4676
    DOI 10.15252/emmm.202012476
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book ; Thesis: Charakterisierung der spezifischen Rolle vom humanen WIPI-1 Protein in intrazellulären Signalkaskaden der Autophagie

    Mauthe, Mario

    2013  

    Author's details vorgelegt von Mario Mauthe
    Language English
    Size getr. Zählung, Ill., graph. Darst.
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Univ., Diss.--Tübingen, 2013
    Note Enth. engl.sprachige Zeitschr.aufsätze
    Database Former special subject collection: coastal and deep sea fishing

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  4. Article: Autophagy in Multiple Sclerosis: Two Sides of the Same Coin.

    Misrielal, Chairi / Mauthe, Mario / Reggiori, Fulvio / Eggen, Bart J L

    Frontiers in cellular neuroscience

    2020  Volume 14, Page(s) 603710

    Abstract: Multiple sclerosis (MS) is a complex auto-immune disorder of the central nervous system (CNS) that involves a range of CNS and immune cells. MS is characterized by chronic neuroinflammation, demyelination, and neuronal loss, but the molecular causes of ... ...

    Abstract Multiple sclerosis (MS) is a complex auto-immune disorder of the central nervous system (CNS) that involves a range of CNS and immune cells. MS is characterized by chronic neuroinflammation, demyelination, and neuronal loss, but the molecular causes of this disease remain poorly understood. One cellular process that could provide insight into MS pathophysiology and also be a possible therapeutic avenue, is autophagy. Autophagy is an intracellular degradative pathway essential to maintain cellular homeostasis, particularly in neurons as defects in autophagy lead to neurodegeneration. One of the functions of autophagy is to maintain cellular homeostasis by eliminating defective or superfluous proteins, complexes, and organelles, preventing the accumulation of potentially cytotoxic damage. Importantly, there is also an intimate and intricate interplay between autophagy and multiple aspects of both innate and adaptive immunity. Thus, autophagy is implicated in two of the main hallmarks of MS, neurodegeneration, and inflammation, making it especially important to understand how this pathway contributes to MS manifestation and progression. This review summarizes the current knowledge about autophagy in MS, in particular how it contributes to our understanding of MS pathology and its potential as a novel therapeutic target.
    Language English
    Publishing date 2020-11-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2020.603710
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Using microbes as a key tool to unravel the mechanism of autophagy and the functions of the ATG proteins.

    Mauthe, Mario / Reggiori, Fulvio

    Microbial cell (Graz, Austria)

    2016  Volume 4, Issue 1, Page(s) 1–5

    Abstract: The study of microbe infections has always been a very effective approach to unveil and dissect cellular pathways. Autophagy is not an exception. Although some of the breakthrough discoveries in the field were obtained using yeast, pathogens have been ... ...

    Abstract The study of microbe infections has always been a very effective approach to unveil and dissect cellular pathways. Autophagy is not an exception. Although some of the breakthrough discoveries in the field were obtained using yeast, pathogens have been and still are a great tool to discover and characterize new molecular and functional aspects of autophagy. Research on pathogens has helped to acquire knowledge about selective types of autophagy and the assembly of the autophagy machinery, i.e the autophagy-related (ATG) proteins, but also about alternative cellular roles of this pathway, such as secretion. Finally, microbes have also served to discover and characterize unconventional functions of the ATG proteins, which are uncoupled from their role in autophagy. In our recent study, we have taken advantage of viruses as a screening tool to determine the extent of the unconventional functions of the ATG proteome and characterize one of them.
    Keywords covid19
    Language English
    Publishing date 2016-12-30
    Publishing country Austria
    Document type Editorial
    ZDB-ID 2814756-X
    ISSN 2311-2638
    ISSN 2311-2638
    DOI 10.15698/mic2017.01.550
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: ATG proteins: Are we always looking at autophagy?

    Mauthe, Mario / Reggiori, Fulvio

    Autophagy

    2016  Volume 12, Issue 12, Page(s) 2502–2503

    Abstract: Autophagy is an intracellular degradation pathway that is regulated by the autophagy-related (ATG) proteins. For a long time it has been thought that ATG proteins were exclusively required for autophagy, but recent experimental evidence has revealed that ...

    Abstract Autophagy is an intracellular degradation pathway that is regulated by the autophagy-related (ATG) proteins. For a long time it has been thought that ATG proteins were exclusively required for autophagy, but recent experimental evidence has revealed that these proteins are part of other cellular pathways, individually or as a functional group. To estimate the extent of these so-called unconventional functions of the ATG proteins, we decided to perform an unbiased siRNA screen targeting the entire ATG proteome and used viral replication as the readout. Our results have uncovered that a surprisingly high number of ATG proteins (36%) have a positive or negative role in promoting virus replication outside their classical role in autophagy. With the increasing knowledge about ATG protein unconventional functions and our investigation results, the interpretations about the possible involvement of autophagy in cellular or organismal functions that solely rely on the depletion of a single ATG protein, should be considered cautiously.
    MeSH term(s) Animals ; Autophagy ; Autophagy-Related Proteins/metabolism ; Humans ; Models, Biological ; Sequence Analysis, RNA ; Virus Diseases/metabolism ; Virus Diseases/pathology ; Virus Replication
    Chemical Substances Autophagy-Related Proteins
    Language English
    Publishing date 2016-09-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2016.1236878
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: HSBP1 Is a Novel Interactor of FIP200 and ATG13 That Promotes Autophagy Initiation and Picornavirus Replication.

    Mauthe, Mario / Dinesh Kumar, Nilima / Verlhac, Pauline / van de Beek, Nicole / Reggiori, Fulvio

    Frontiers in cellular and infection microbiology

    2021  Volume 11, Page(s) 745640

    Abstract: ATG13 and FIP200 are two subunits of the ULK kinase complex, a key regulatory component of the autophagy machinery. We have previously found that the FIP200-ATG13 subcomplex controls picornavirus replication outside its role in the ULK kinase complex and ...

    Abstract ATG13 and FIP200 are two subunits of the ULK kinase complex, a key regulatory component of the autophagy machinery. We have previously found that the FIP200-ATG13 subcomplex controls picornavirus replication outside its role in the ULK kinase complex and autophagy. Here, we characterized HSBP1, a very small cytoplasmic coiled-coil protein, as a novel interactor of FIP200 and ATG13 that binds these two proteins
    MeSH term(s) Autophagy ; Autophagy-Related Proteins/genetics ; Cell Cycle Proteins ; Picornaviridae/genetics ; Transcription Factors
    Chemical Substances Autophagy-Related Proteins ; Cell Cycle Proteins ; Transcription Factors
    Language English
    Publishing date 2021-11-15
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2021.745640
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: WDR45

    Cong, Yingying / So, Vincent / Tijssen, Marina A J / Verbeek, Dineke S / Reggiori, Fulvio / Mauthe, Mario

    Autophagy

    2021  Volume 17, Issue 12, Page(s) 3908–3923

    Abstract: ... ...

    Abstract The
    MeSH term(s) Autophagy/genetics ; Carrier Proteins/metabolism ; Humans ; Macroautophagy ; Neurodegenerative Diseases/metabolism ; Neurodevelopmental Disorders/genetics
    Chemical Substances Carrier Proteins ; WDR45 protein, human
    Language English
    Publishing date 2021-04-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2021.1899669
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  9. Article ; Online: Transcriptomic changes in autophagy-related genes are inversely correlated with inflammation and are associated with multiple sclerosis lesion pathology.

    Misrielal, Chairi / Alsema, Astrid M / Wijering, Marion H C / Miedema, Anneke / Mauthe, Mario / Reggiori, Fulvio / Eggen, Bart J L

    Brain, behavior, & immunity - health

    2022  Volume 25, Page(s) 100510

    Abstract: Autophagy is a lysosomal degradative pathway essential for maintaining cellular homeostasis and is also implicated in multiple aspects of both innate and adaptive immunity. Neuroinflammation, along with demyelination and axonal loss, is an important ... ...

    Abstract Autophagy is a lysosomal degradative pathway essential for maintaining cellular homeostasis and is also implicated in multiple aspects of both innate and adaptive immunity. Neuroinflammation, along with demyelination and axonal loss, is an important component of multiple sclerosis (MS). Induction of autophagy ameliorated disease progression in experimental autoimmune encephalomyelitis (EAE), a mouse model for MS, underlying a possible link between autophagy and MS pathology. However, it is still unclear how autophagy is affected during different stages of MS. Here, we show a decreased expression of the
    Language English
    Publishing date 2022-09-08
    Publishing country United States
    Document type Journal Article
    ISSN 2666-3546
    ISSN (online) 2666-3546
    DOI 10.1016/j.bbih.2022.100510
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Manipulation of selective macroautophagy by pathogens at a glance.

    Cong, Yingying / Dinesh Kumar, Nilima / Mauthe, Mario / Verlhac, Pauline / Reggiori, Fulvio

    Journal of cell science

    2020  Volume 133, Issue 10

    Abstract: Macroautophagy (hereafter autophagy) is a highly conserved catabolic pathway, which mediates the delivery of unwanted cytoplasmic structures and organelles to lysosomes for degradation. In numerous situations, autophagy is highly selective and ... ...

    Abstract Macroautophagy (hereafter autophagy) is a highly conserved catabolic pathway, which mediates the delivery of unwanted cytoplasmic structures and organelles to lysosomes for degradation. In numerous situations, autophagy is highly selective and exclusively targets specific intracellular components. Selective types of autophagy are a central element of our cell-autonomous innate immunity as they can mediate the turnover of viruses or bacteria, that gain access to the cytoplasm of the cell. Selective autophagy also modulates other aspects of our immunity by turning over specific immunoregulators. Throughout evolution, however, the continuous interaction between this fundamental cellular pathway and pathogens has led several pathogens to develop exquisite mechanisms to inhibit or subvert selective types of autophagy, to promote their intracellular multiplication. This Cell Science at a Glance article and the accompanying poster provides an overview of the selective autophagy of both pathogens, known as xenophagy, and of immunoregulators, and highlights a few archetypal examples that illustrate molecular strategies developed by viruses and bacteria to manipulate selective autophagy for their own benefit.
    MeSH term(s) Autophagy ; Bacteria ; Immunity, Innate ; Lysosomes ; Macroautophagy ; Viruses
    Language English
    Publishing date 2020-05-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.240440
    Database MEDical Literature Analysis and Retrieval System OnLINE

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