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https://www.readbyqxmd.com/read/29909986/mitophagy-in-intestinal-epithelial-cells-triggers-adaptive-immunity-during-tumorigenesis
#1
Paul K Ziegler, Julia Bollrath, Charles K Pallangyo, Takaji Matsutani, Özge Canli, Tiago De Oliveira, Michaela A Diamanti, Nina Müller, Jaba Gamrekelashvili, Tracy Putoczki, David Horst, Arun K Mankan, Meryem G Öner, Susanna Müller, Josef Müller-Höcker, Thomas Kirchner, Julia Slotta-Huspenina, M Mark Taketo, Thomas Reinheckel, Stefan Dröse, Andrew C Larner, Winfried S Wels, Matthias Ernst, Tim F Greten, Melek C Arkan, Thomas Korn, Dagmar Wirth, Florian R Greten
In colorectal cancer patients, a high density of cytotoxic CD8+ T cells in tumors is associated with better prognosis. Using a Stat3 loss-of-function approach in two wnt/β-catenin-dependent autochthonous models of sporadic intestinal tumorigenesis, we unravel a complex intracellular process in intestinal epithelial cells (IECs) that controls the induction of a CD8+ T cell based adaptive immune response. Elevated mitophagy in IECs causes iron(II)-accumulation in epithelial lysosomes, in turn, triggering lysosomal membrane permeabilization...
June 11, 2018: Cell
https://www.readbyqxmd.com/read/29895192/viral-strategies-for-triggering-and-manipulating-mitophagy
#2
Linliang Zhang, Yali Qin, Mingzhou Chen
Viral infection causes many physiological alterations in the host cell, and many of these alterations can affect the host mitochondrial network, including mitophagy induction. A substantial amount of literature has been generated that advances our understanding of the relationship between mitophagy and several viruses. Some viruses trigger mitophagy directly, and indirectly and control the mitophagic process via different strategies. This enables viruses to promote persistent infection and attenuate the innate immune responses...
June 12, 2018: Autophagy
https://www.readbyqxmd.com/read/29764564/mitochondria-mediated-defense-mechanisms-against-pathogens-in-caenorhabditis-elegans
#3
Sujeong Kwon, Eun Ji E Kim, Seung-Jae V Lee
Mitochondria are crucial organelles that generate cellular energy and metabolites. Recent studies indicate that mitochondria also regulate immunity. In this review, we discuss key roles of mitochondria in immunity against pathogen infection and underlying mechanisms, focusing on discoveries using Caenorhabditis elegans. Various mitochondrial processes, including mitochondrial surveillance mechanisms, mitochondrial unfolded protein response (UPRmt), mitophagy, and reactive oxygen species (ROS) production, contribute to immune responses and resistance of C...
May 16, 2018: BMB Reports
https://www.readbyqxmd.com/read/29723606/salidroside-mediated-stabilization-of-bcl-x-l-prevents-mitophagy-in-ca3-hippocampal-neurons-during-hypoxia
#4
Suryanarayan Biswal, Kalpana Kumari Barhwal, Debashree Das, Richa Dhingra, Nilima Dhingra, Tapas Chanda Nag, Sunil Kumar Hota
Chronic hypoxic stress results in deposition of lipofuscin granules in the CA3 region of hippocampal neurons which contributes to neurodegeneration and accelerated neuronal aging. Oxidative stress and mitophagy during hypoxia are crucial to cause aggregation of these lipofuscin granules in hypoxic neurons. Salidroside, a glucoside derivative of β-Tyrosol, has been reported to protect hypoxic neurons through maintenance of mitochondrial activity. The present study is aimed at investigating the potential of Salidroside in preventing mitophagy during chronic hypoxia and identification of the molecular targets and underlying signaling mechanisms...
April 30, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29599894/emerging-players-at-the-intersection-of-chondrocyte-loss-of-maturational-arrest-oxidative-stress-senescence-and-low-grade-inflammation-in-osteoarthritis
#5
REVIEW
Manuela Minguzzi, Silvia Cetrullo, Stefania D'Adamo, Ylenia Silvestri, Flavio Flamigni, Rosa Maria Borzì
The prevalence of Osteoarthritis (OA) is increasing because of the progressive aging and unhealthy lifestyle. These risk factors trigger OA by removing constraints that keep the tightly regulated low turnover of the extracellular matrix (ECM) of articular cartilage, the correct chondrocyte phenotype, and the functionality of major homeostatic mechanisms, such as mitophagy, that allows for the clearance of dysfunctional mitochondria, preventing increased production of reactive oxygen species, oxidative stress, and senescence...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29581312/-s-nitrosylation-drives-cell-senescence-and-aging-in-mammals-by-controlling-mitochondrial-dynamics-and-mitophagy
#6
Salvatore Rizza, Simone Cardaci, Costanza Montagna, Giuseppina Di Giacomo, Daniela De Zio, Matteo Bordi, Emiliano Maiani, Silvia Campello, Antonella Borreca, Annibale A Puca, Jonathan S Stamler, Francesco Cecconi, Giuseppe Filomeni
S -nitrosylation, a prototypic redox-based posttranslational modification, is frequently dysregulated in disease. S -nitrosoglutathione reductase (GSNOR) regulates protein S -nitrosylation by functioning as a protein denitrosylase. Deficiency of GSNOR results in tumorigenesis and disrupts cellular homeostasis broadly, including metabolic, cardiovascular, and immune function. Here, we demonstrate that GSNOR expression decreases in primary cells undergoing senescence, as well as in mice and humans during their life span...
April 10, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29515999/emerging-mechanisms-of-innate-immunity-and-their-translational-potential-in-inflammatory-bowel-disease
#7
REVIEW
Daniele Corridoni, Thomas Chapman, Tim Ambrose, Alison Simmons
Activation of the innate immune system through pattern-recognition receptor (PRR) signaling plays a pivotal role in the early induction of host defense following exposure to pathogens. Loss of intestinal innate immune regulation leading aberrant immune responses has been implicated in the pathogenesis of inflammatory bowel disease (IBD). The precise role of PRRs in gut inflammation is not well understood, but considering their role as bacterial sensors and their genetic association with IBD, they likely contribute to dysregulated immune responses to the commensal microbiota...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29511917/the-role-of-mitochondria-in-cellular-toxicity-as-a-potential-drug-target
#8
EDITORIAL
Duojiao Wu, Xiangdong Wang, Hongzhi Sun
Mitochondrial malfunction is related to aging and to the onset of many diseases, such as obesity/diabetes, cancer, and cardiovascular and neurodegenerative diseases. The molecular principles of biological and toxicological processes the mitochondria can regulate should be disease-specific, cell type-specific, and drug targetable. Mitochondrial biology and toxicology is evolving and undergoing a revolution through fast-developing biotechnologies garnering increasing attention due to the importance of targeted therapies...
April 2018: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/29488209/decorin-mediated-oncosuppression-a-potential-future-adjuvant-therapy-for-human-epithelial-cancers
#9
REVIEW
Annele Orvokki Sainio, Hannu Tapio Järveläinen
Currently, the multifaceted role of the extracellular matrix (ECM) in tumourigenesis has been realized. One ECM macromolecule exhibiting potent oncosuppressive actions in tumourigenesis is decorin, the prototype of the small leucine-rich proteoglycan gene family. The actions of decorin include its ability to function as an endogenous pan-receptor tyrosine kinase inhibitor, a regulator of both autophagy and mitophagy, as well as a modulator of the immune system. In this review, we will discuss these topics in more detail...
February 27, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29463101/autophagy-a-lysosome-dependent-process-with-implications-in-cellular-redox-homeostasis-and-human-disease
#10
Stefan W Ryter, Divya Bhatia, Mary E Choi
SIGNIFICANCE: Autophagy, a lysosome-dependent homeostatic process inherent to cells and tissues, has emerging significance in the pathogenesis of human disease. This process enables the degradation and turnover of cytoplasmic substrates via membrane-dependent sequestration in autophagic vesicles (autophagosomes) and subsequent lysosomal delivery of cargo. Recent Advances: Selective forms of autophagy can target specific substrates (e.g., organelles, protein aggregates, and lipids) for processing...
March 28, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29402601/mitophagy-in-three-cases-of-immune-mediated-necrotizing-myopathy-associated-with-anti-3-hydroxy-3-methylglutaryl-coenzyme-a-reductase-autoantibodies-ultrastructural-and-immunohistochemical-studies
#11
Shiro Matsubara, Kota Bokuda, Yuri Asano, Ryo Morishima, Keizo Sugaya, Kazuhito Miyamoto, Reiji Koide, Takashi Komori, Shigeaki Suzuki, Ichizo Nishino
Immune-mediated necrotizing myopathy (IMNM) associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies occurs in patients both with and without history of statin-intake. The mechanisms of muscle fiber degeneration in this condition remain unknown. We studied pathological changes in muscle biopsies from three patients lacking history of statin-intake. Ultrastructural observations showed accumulation of degenerating mitochondria, glycogen granules and autophagic vacuoles, forming large composites in three cases, along with various nonspecific changes...
March 2018: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/29374208/down-regulation-of-guanylate-binding-protein-1-causes-mitochondrial-dysfunction-and-cellular-senescence-in-macrophages
#12
Xiaoxue Qiu, Hong Guo, Junshu Yang, Yinduo Ji, Chia-Shan Wu, Xiaoli Chen
Macrophage polarization is tightly associated with its metabolic reprograming and immune dysfunction. However, the intracellular molecules/pathways that connect these alterations in inflammatory macrophages remain largely unidentified. Herein, we explored the role of guanylate binding protein 1 (Gbp1), an intracellular anti-microbial protein, in regulating polarization, metabolic reprogramming, and cellular aging of macrophages. We showed that Gbp1 expression in inguinal white adipose tissue is significantly decreased in high-fat diet -fed and aged mice...
January 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29369001/itraq-based-proteomics-analysis-of-autophagy-mediated-immune-responses-against-the-vascular-fungal-pathogen-verticillium-dahliae-in-arabidopsis
#13
Fu-Xin Wang, Yuan-Ming Luo, Zi-Qin Ye, Xue Cao, Jing-Nan Liang, Qian Wang, Yao Wu, Jia-He Wu, Hai-Yun Wang, Min Zhang, Huan-Qing Cheng, Gui-Xian Xia
The mechanisms underlying the functional link between autophagy and plant innate immunity remain largely unknown. In this study, we investigated the autophagy-mediated plant defense responses against Verticillium dahliae (V. dahliae) infection by comparative proteomics and cellular analyses. An assessment of the autophagy activity and disease development showed that autophagic processes were tightly related to the tolerance of Arabidopsis plant to Verticillium wilt. An isobaric tags for relative and absolute quantification (iTRAQ)-based proteomics analysis was performed, and we identified a total of 780 differentially accumulated proteins (DAPs) between wild-type and mutant atg10-1 Arabidopsis plants upon V...
January 25, 2018: Autophagy
https://www.readbyqxmd.com/read/29345056/for-when-bacterial-infections-persist-toll-like-receptor-inducible-direct-antimicrobial-pathways-in-macrophages
#14
REVIEW
Claudia J Stocks, Mark A Schembri, Matthew J Sweet, Ronan Kapetanovic
Macrophages are linchpins of innate immunity, responding to invading microorganisms by initiating coordinated inflammatory and antimicrobial programs. Immediate antimicrobial responses, such as NADPH-dependent reactive oxygen species (ROS), are triggered upon phagocytic receptor engagement. Macrophages also detect and respond to microbial products through pattern recognition receptors (PRRs), such as TLRs. TLR signaling influences multiple biological processes including antigen presentation, cell survival, inflammation, and direct antimicrobial responses...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29107116/mitophagy-and-the-release-of-inflammatory-cytokines
#15
REVIEW
James Harris, Nadia Deen, Shahrzad Zamani, Md Abul Hasnat
Mitophagy is a selective form of autophagy in which damaged or dysfunctional mitochondria are specifically targeted by autophagosomes for lysosomal degradation. Studies have demonstrated that loss of autophagy/mitophagy can lead to a build-up of cytosolic reactive oxygen species and mitochondrial DNA, which can, in turn, activate immune signalling pathways that ultimately lead to the releases of inflammatory cytokines, including IL-1α, IL-1β, IL-18 and macrophage migration inhibitory factor (MIF). Moreover, release of these cytokines can subsequently promote the release of others, including IL-23 and IL-17...
October 26, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29077752/isg15-governs-mitochondrial-function-in-macrophages-following-vaccinia-virus-infection
#16
Sara Baldanta, Mercedes Fernández-Escobar, Rebeca Acín-Perez, Manuel Albert, Emilio Camafeita, Inmaculada Jorge, Jesús Vázquez, José Antonio Enríquez, Susana Guerra
The interferon (IFN)-stimulated gene 15 (ISG15) encodes one of the most abundant proteins induced by interferon, and its expression is associated with antiviral immunity. To identify protein components implicated in IFN and ISG15 signaling, we compared the proteomes of ISG15-/- and ISG15+/+ bone marrow derived macrophages (BMDM) after vaccinia virus (VACV) infection. The results of this analysis revealed that mitochondrial dysfunction and oxidative phosphorylation (OXPHOS) were pathways altered in ISG15-/- BMDM treated with IFN...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29054471/innate-immunity-and-tolerance-toward-mitochondria
#17
REVIEW
Anthony Rongvaux
Mitochondria are intracellular organelles that originate from a bacterial symbiont, and they retain multiple features of this bacterial ancestry. The immune system evolved to detect the presence of invading pathogens, including bacteria, to eliminate them by a diversity of antimicrobial mechanisms and to mount long-term protective immunity. Due to their bacterial ancestry, mitochondria are sensed by the innate immune system, and trigger inflammatory responses comparable to those induced by pathogenic bacteria...
October 17, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29049365/myd88-dependent-inflammasome-activation-and-autophagy-inhibition-contributes-to-ehrlichia-induced-liver-injury-and-toxic-shock
#18
Muhamuda Kader, Mounia Alaoui-El-Azher, Jennie Vorhauer, Bhushan B Kode, Jakob Z Wells, Donna Stolz, George Michalopoulos, Alan Wells, Melanie Scott, Nahed Ismail
Severe hepatic inflammation is a common cause of acute liver injury following systemic infection with Ehrlichia, obligate Gram-negative intracellular bacteria that lack lipopolysaccharide (LPS). We have previously shown that type I IFN (IFN-I) and inflammasome activation are key host-pathogenic mediators that promote excessive inflammation and liver damage following fatal Ehrlichia infection. However, the underlying signals and mechanisms that regulate protective immunity and immunopathology during Ehrlichia infection are not well understood...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28978702/coxsackievirus-b-escapes-the-infected-cell-in-ejected-mitophagosomes
#19
Jon Sin, Laura McIntyre, Aleksandr Stotland, Ralph Feuer, Roberta A Gottlieb
Coxsackievirus B (CVB) is a common enterovirus that can cause various systemic inflammatory diseases. Because CVB lacks an envelope, it has been thought to be inherently cytolytic, wherein CVB can escape from the infected host cell only by causing it to rupture. In recent years, however, we and others have observed that various naked viruses, such as CVB, can trigger the release of infectious extracellular microvesicles (EMVs) that contain viral material. This mode of cellular escape has been suggested to allow the virus to be masked from the adaptive immune system...
December 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768533/progression-of-pathology-in-pink1-deficient-mouse-brain-from-splicing-via-ubiquitination-er-stress-and-mitophagy-changes-to-neuroinflammation
#20
Sylvia Torres-Odio, Jana Key, Hans-Hermann Hoepken, Júlia Canet-Pons, Lucie Valek, Bastian Roller, Michael Walter, Blas Morales-Gordo, David Meierhofer, Patrick N Harter, Michel Mittelbronn, Irmgard Tegeder, Suzana Gispert, Georg Auburger
BACKGROUND: PINK1 deficiency causes the autosomal recessive PARK6 variant of Parkinson's disease. PINK1 activates ubiquitin by phosphorylation and cooperates with the downstream ubiquitin ligase PARKIN, to exert quality control and control autophagic degradation of mitochondria and of misfolded proteins in all cell types. METHODS: Global transcriptome profiling of mouse brain and neuron cultures were assessed in protein-protein interaction diagrams and by pathway enrichment algorithms...
August 2, 2017: Journal of Neuroinflammation
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