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Xenophagy

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https://www.readbyqxmd.com/read/28806134/ilir-viral-a-web-resource-for-lir-motif-containing-proteins-in-viruses
#1
Anne-Claire Jacomin, Siva Samavedam, Hannah Charles, Ioannis P Nezis
Macroautophagy/autophagy has been shown to mediate the selective lysosomal degradation of pathogenic bacteria and viruses (xenophagy), and to contribute to the activation of innate and adaptative immune responses. Autophagy can serve as an antiviral defense mechanism but also as a pro-viral process during infection. Atg8-family proteins play a central role in the autophagy process due to their ability to interact with components of the autophagy machinery as well as selective autophagy receptors and adaptor proteins...
August 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28799902/innate-immunity-to-intracellular-pathogens-balancing-microbial-elimination-and-inflammation
#2
REVIEW
Gabriel Mitchell, Ralph R Isberg
Recent excitement regarding immune clearance of intracellular microorganisms has focused on two systems that maintain cellular homeostasis. One system includes cellular autophagy components that mediate degradation of pathogens in membrane-bound compartments, in a process termed xenophagy. The second system is driven by interferon-regulated GTPases that promote rupture of pathogen-containing vacuoles and microbial degradation. In the case of xenophagy, pathogen sequestration and compartmentalization suppress inflammation...
August 9, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28685931/structure-of-the-wd40-domain-of-human-atg16l1
#3
Milica Bajagic, Archna, Petra Büsing, Andrea Scrima
Autophagy-related protein ATG16L1 is a component of the mammalian ATG12∼ATG5/ATG16L1 complex, which acts as E3-ligase to catalyze lipidation of LC3 during autophagosome biogenesis. The N-terminal part of ATG16L1 comprises the ATG5-binding site and coiled-coil dimerization domain, both also present in yeast ATG16 and essential for bulk and starvation induced autophagy. While absent in yeast ATG16, mammalian ATG16L1 further contains a predicted C-terminal WD40-domain, which has been shown to be involved in mediating interaction with diverse factors in the context of alternative functions of autophagy, such as inflammatory control and xenophagy...
July 7, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28683091/endothelial-cells-are-intrinsically-defective-in-xenophagy-of-streptococcus-pyogenes
#4
Shiou-Ling Lu, Tsuyoshi Kawabata, Yi-Lin Cheng, Hiroko Omori, Maho Hamasaki, Tatsuya Kusaba, Ryo Iwamoto, Hirokazu Arimoto, Takeshi Noda, Yee-Shin Lin, Tamotsu Yoshimori
Group A Streptococcus (GAS) is deleterious pathogenic bacteria whose interaction with blood vessels leads to life-threatening bacteremia. Although xenophagy, a special form of autophagy, eliminates invading GAS in epithelial cells, we found that GAS could survive and multiply in endothelial cells. Endothelial cells were competent in starvation-induced autophagy, but failed to form double-membrane structures surrounding GAS, an essential step in xenophagy. This deficiency stemmed from reduced recruitment of ubiquitin and several core autophagy proteins in endothelial cells, as demonstrated by the fact that it could be rescued by exogenous coating of GAS with ubiquitin...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28634388/mito-xenophagic-killing-of-bacteria-is-coordinated-by-a-metabolic-switch-in-dendritic-cells
#5
Nadine Radomski, Danny Kägebein, Elisabeth Liebler-Tenorio, Axel Karger, Elke Rufer, Birke Andrea Tews, Stefanie Nagel, Rebekka Einenkel, Anne Müller, Annica Rebbig, Michael R Knittler
Chlamydiae are bacterial pathogens that grow in vacuolar inclusions. Dendritic cells (DCs) disintegrate these compartments, thereby eliminating the microbes, through auto/xenophagy, which also promotes chlamydial antigen presentation via MHC I. Here, we show that TNF-α controls this pathway by driving cytosolic phospholipase (cPLA)2-mediated arachidonic acid (AA) production. AA then impairs mitochondrial function, which disturbs the development and integrity of these energy-dependent parasitic inclusions, while a simultaneous metabolic switch towards aerobic glycolysis promotes DC survival...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28481361/linear-ubiquitination-of-cytosolic-salmonella-typhimurium-activates-nf-%C3%AE%C2%BAb-and-restricts-bacterial-proliferation
#6
Sjoerd J L van Wijk, Franziska Fricke, Lina Herhaus, Jalaj Gupta, Katharina Hötte, Francesco Pampaloni, Paolo Grumati, Manuel Kaulich, Yu-Shin Sou, Masaaki Komatsu, Florian R Greten, Simone Fulda, Mike Heilemann, Ivan Dikic
Ubiquitination of invading Salmonella Typhimurium triggers autophagy of cytosolic bacteria and restricts their spread in epithelial cells. Ubiquitin (Ub) chains recruit autophagy receptors such as p62/SQSTM1, NDP52/CALCOCO and optineurin (OPTN), which initiate the formation of double-membrane autophagosomal structures and lysosomal destruction in a process known as xenophagy. Besides this, the functional consequences and mechanistic regulation of differentially linked Ub chains at the host-Salmonella interface have remained unexplored...
May 8, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28481331/lubac-synthesized-linear-ubiquitin-chains-restrict-cytosol-invading-bacteria-by-activating-autophagy-and-nf-%C3%AE%C2%BAb
#7
Jessica Noad, Alexander von der Malsburg, Claudio Pathe, Martin A Michel, David Komander, Felix Randow
Cell-autonomous immunity relies on the ubiquitin coat surrounding cytosol-invading bacteria functioning as an 'eat-me' signal for xenophagy. The origin, composition and precise mode of action of the ubiquitin coat remain incompletely understood. Here, by studying Salmonella Typhimurium, we show that the E3 ligase LUBAC generates linear (M1-linked) polyubiquitin patches in the ubiquitin coat, which serve as antibacterial and pro-inflammatory signalling platforms. LUBAC is recruited via its subunit HOIP to bacterial surfaces that are no longer shielded by host membranes and are already displaying ubiquitin, suggesting that LUBAC amplifies and refashions the ubiquitin coat...
May 8, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28456980/lysophagy-a-method-for-monitoring-lysosomal-rupture-followed-by-autophagy-dependent-recovery
#8
Takanobu Otomo, Tamotsu Yoshimori
Selective autophagy recognizes specific targets, including damaged mitochondria (mitophagy), aggregated proteins (aggrephagy), and invading bacteria (xenophagy) to engulf by isolation membrane, and degrades toxic materials within lysosomes. We recently revealed that a membrane-damaged lysosome itself also becomes a target of autophagy and named this process lysophagy. In this chapter, we describe methods for monitoring lysophagy; detecting lysosomal damage by staining of galectin and study the subsequent autophagic process in cultured mammalian cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28367819/-autophagy-atg-proteins-and-infectious-diseases
#9
Isabelle Vergne, Frank Lafont, Lucile Espert, Audrey Esclatine, Martine Biard-Piechaczyk
One of the main functions of the autophagy pathway is to control infections. Intracellular micro-organisms or their products once internalized in the host cell can be directly degraded by autophagy, a process called xenophagy. Autophagy is also involved in other innate immune responses and participates to the adaptive immune system. In addition, several autophagy proteins play a role in the development of infectious diseases independently of their role in the autophagy pathway. To replicate efficiently, pathogens have therefore evolved to counteract this process or to exploit it to their own profit...
March 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28213625/8-nitro-cgmp-a-novel-protein-reactive-cnmp-and-its-emerging-roles-in-autophagy
#10
Hirokazu Arimoto, Daiki Takahashi
Nitric oxide (NO) raises the intracellular 3',5'-cyclic guanosine monophosphate (cGMP) level through the activation of soluble guanylate cyclase and, in the presence of reactive oxygen species (ROS), reacts with biomolecules to produce nitrated cGMP derivatives. 8-Nitro-cGMP was the first endogenous cGMP derivative discovered in mammalian cells (2007) and was later found in plant cells. Among the six nitrogen atoms in this molecule, the one in the nitro group (NO2) comes from NO. This chapter asserts that this newly found cGMP is undoubtedly one of the major physiological cNMPs...
2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28028054/fluorescence-based-atg8-sensors-monitor-localization-and-function-of-lc3-gabarap-proteins
#11
Alexandra Stolz, Mateusz Putyrski, Ivana Kutle, Jessica Huber, Chunxin Wang, Viktória Major, Sachdev S Sidhu, Richard J Youle, Vladimir V Rogov, Volker Dötsch, Andreas Ernst, Ivan Dikic
Autophagy is a cellular surveillance pathway that balances metabolic and energy resources and transports specific cargos, including damaged mitochondria, other broken organelles, or pathogens for degradation to the lysosome. Central components of autophagosomal biogenesis are six members of the LC3 and GABARAP family of ubiquitin-like proteins (mATG8s). We used phage display to isolate peptides that possess bona fide LIR (LC3-interacting region) properties and are selective for individual mATG8 isoforms. Sensitivity of the developed sensors was optimized by multiplication, charge distribution, and fusion with a membrane recruitment (FYVE) or an oligomerization (PB1) domain...
February 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28026986/xenophagy-a-battlefield-between-host-and-microbe-and-a-possible-avenue-for-cancer-treatment
#12
Kai Mao, Daniel J Klionsky
In eukaryotes, xenophagy is defined as a type of selective macroautophagy/autophagy that is used for eliminating invading pathogens. In contrast to other types of selective autophagy, such as mitophagy, pexophagy and ribophagy, xenophagy is used by eukaryotes for targeting microbes-hence the prefix "xeno" meaning "other" or "foreign"-that have infected a host cell, leading to their lysosomal degradation. This unique characteristic links xenophagy to antibacterial and antiviral defenses, as well as the immune response...
February 2017: Autophagy
https://www.readbyqxmd.com/read/27924676/bacterial-xenophagy-and-its-possible-role-in-cancer-a-potential-antimicrobial-strategy-for-cancer-prevention-and-treatment
#13
Xinbing Sui, Xiao Liang, Liuxi Chen, Chunming Guo, Weidong Han, Hongming Pan, Xue Li
Macroautophagy/autophagy is a conserved catabolic process through which cellular excessive or dysfunctional proteins and organelles are transported to the lysosome for terminal degradation and recycling. Over the past few years increasing evidence has suggested that autophagy is not only a simple metabolite recycling mechanism, but also plays a critical role in the removal of intracellular pathogens such as bacteria and viruses. When autophagy engulfs intracellular pathogens, the pathway is called 'xenophagy' because it leads to the elimination of foreign microbes...
February 2017: Autophagy
https://www.readbyqxmd.com/read/27906974/in-silico-knockout-studies-of-xenophagic-capturing-of-salmonella
#14
Jennifer Scheidel, Leonie Amstein, Jörg Ackermann, Ivan Dikic, Ina Koch
The degradation of cytosol-invading pathogens by autophagy, a process known as xenophagy, is an important mechanism of the innate immune system. Inside the host, Salmonella Typhimurium invades epithelial cells and resides within a specialized intracellular compartment, the Salmonella-containing vacuole. A fraction of these bacteria does not persist inside the vacuole and enters the host cytosol. Salmonella Typhimurium that invades the host cytosol becomes a target of the autophagy machinery for degradation...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27880896/rnf166-determines-recruitment-of-adaptor-proteins-during-antibacterial-autophagy
#15
Robert J Heath, Gautam Goel, Leigh A Baxt, Jason S Rush, Vishnu Mohanan, Geraldine L C Paulus, Vijay Jani, Kara G Lassen, Ramnik J Xavier
Xenophagy is a form of selective autophagy that involves the targeting and elimination of intracellular pathogens through several recognition, recruitment, and ubiquitination events. E3 ubiquitin ligases control substrate selectivity in the ubiquitination cascade; however, systematic approaches to map the role of E3 ligases in antibacterial autophagy have been lacking. We screened more than 600 putative human E3 ligases, identifying E3 ligases that are required for adaptor protein recruitment and LC3-bacteria colocalization, critical steps in antibacterial autophagy...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27866924/bacterial-pathogens-versus-autophagy-implications-for-therapeutic-interventions
#16
REVIEW
Jacqueline M Kimmey, Christina L Stallings
Research in recent years has focused significantly on the role of selective macroautophagy in targeting intracellular pathogens for lysosomal degradation, a process termed xenophagy. In this review we evaluate the proposed roles for xenophagy in controlling bacterial infection, highlighting the concept that successful pathogens have evolved ways to subvert or exploit this defense, minimizing the actual effectiveness of xenophagy in innate immunity. Instead, studies in animal models have revealed that autophagy-associated proteins often function outside of xenophagy to influence bacterial pathogenesis...
December 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27791468/the-stx6-vti1b-vamp3-complex-facilitates-xenophagy-by-regulating-the-fusion-between-recycling-endosomes-and-autophagosomes
#17
Takashi Nozawa, Atsuko Minowa-Nozawa, Chihiro Aikawa, Ichiro Nakagawa
Macroautophagy/autophagy plays a critical role in immunity by directly degrading invading pathogens such as Group A Streptococcus (GAS), through a process that has been named xenophagy. We previously demonstrated that autophagic vacuoles directed against GAS, termed GAS-containing autophagosome-like vacuoles (GcAVs), use recycling endosomes (REs) as a membrane source. However, the precise molecular mechanism that facilitates the fusion between GcAVs and REs remains unclear. Here, we demonstrate that STX6 (syntaxin 6) is recruited to GcAVs and forms a complex with VTI1B and VAMP3 to regulate the GcAV-RE fusion that is required for xenophagy...
January 2, 2017: Autophagy
https://www.readbyqxmd.com/read/27485662/intracellular-salmonella-induces-aggrephagy-of-host-endomembranes-in-persistent-infections
#18
Noelia López-Montero, Estel Ramos-Marquès, Cristina Risco, Francisco García-Del Portillo
Xenophagy has been studied in epithelial cells infected with Salmonella enterica serovar Typhimurium (S. Typhimurium). Distinct autophagy receptors target this pathogen to degradation after interacting with ubiquitin on the surface of cytosolic bacteria, and the phagophore- and autophagosome-associated protein MAP1LC3/LC3. Glycans exposed in damaged phagosomal membranes and diacylglycerol accumulation in the phagosomal membrane also trigger S. Typhimurium xenophagy. How these responses control intraphagosomal and cytosolic bacteria remains poorly understood...
October 2, 2016: Autophagy
https://www.readbyqxmd.com/read/27467224/unveiling-ubiquitinome-rearrangements-induced-by-salmonella-infection
#19
Tihana Bionda, Christian Behrends
Ubiquitination plays a critical role in the activation of host immune responses to infection and serves as a signal for pathogen delivery to phagophores along the xenophagy pathway. We recently performed systematic ubiquitination site profiling of epithelial cells infected with Salmonella Typhimurium. Our findings specifically highlight components of the NFKB, membrane trafficking pathways and RHO GTPase systems as ubiquitination hubs during infection. In addition, a broad spectrum of bacterial effectors and several outer membrane proteins are ubiquitinated in infected cells...
September 2016: Autophagy
https://www.readbyqxmd.com/read/27456933/avoidance-and-subversion-of-eukaryotic-homeostatic-autophagy-mechanisms-by-bacterial-pathogens
#20
REVIEW
Cheryl Miller, Jean Celli
Autophagy is a conserved lysosomal recycling process, which maintains cellular homeostasis during stress and starvation conditions by degrading and recycling proteins, lipids, and carbohydrates, ultimately increasing nutrient availability in eukaryotes. An additional function of autophagy, termed xenophagy, is to detect, capture, and destroy invading microorganisms, such as viruses, bacteria, and protozoa, providing autophagy with a role in innate immunity. Many intracellular pathogens have, however, developed mechanisms to avoid xenophagy and have evolved strategies to take advantage of select autophagic processes to undergo their intracellular life cycle...
August 28, 2016: Journal of Molecular Biology
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