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https://www.readbyqxmd.com/read/30215534/the-autophagy-receptor-sqstm1-p62-mediates-anti-inflammatory-actions-of-the-selective-nr3c1-glucocorticoid-receptor-modulator-compound-a-cpda-in-macrophages
#1
Viacheslav Mylka, Julie Deckers, Dariusz Ratman, Lode De Cauwer, Jonathan Thommis, Riet De Rycke, Francis Impens, Claude Libert, Jan Tavernier, Wim Vanden Berghe, Kris Gevaert, Karolien De Bosscher
Glucocorticoids are widely used to treat inflammatory disorders; however, prolonged use of glucocorticoids results in side effects including osteoporosis, diabetes and obesity. Compound A (CpdA), identified as a selective NR3C1/glucocorticoid receptor (nuclear receptor subfamily 3, group C, member 1) modulator, exhibits an inflammation-suppressive effect, largely in the absence of detrimental side effects. To understand the mechanistic differences between the classic glucocorticoid dexamethasone (DEX) and CpdA, we looked for proteins oppositely regulated in bone marrow-derived macrophages using an unbiased proteomics approach...
September 14, 2018: Autophagy
https://www.readbyqxmd.com/read/30215288/palmitoylation-controls-trafficking-of-the-intracellular-ca-2-channel-mcoln3-trpml3-to-regulate-autophagy
#2
So Woon Kim, Dong Hyun Kim, Kyoung Sun Park, Mi Kyung Kim, Yun Min Park, Shmuel Muallem, Insuk So, Hyun Jin Kim
MCOLN3/TRPML3 is a Ca2+ -permeable cation channel that is expressed in multiple subcellular compartments with dynamic localization. Our previous studies suggest that upon macroautophagy/autophagy induction MCOLN3/TRPML3 is recruited and provides Ca2+ for the fusion process in autophagosome biogenesis. However, how intracellular trafficking and the Ca2+ channel function of MCOLN3/TRPML3 are related to autophagy are not known. Here we report that MCOLN3/TRPML3 undergoes palmitoylation at its C-terminal region, which is required for dynamic trafficking and cellular function of MCOLN3/TRPML3 in autophagy...
September 14, 2018: Autophagy
https://www.readbyqxmd.com/read/30209981/darkening-with-uvrag
#3
Shun Li, Gyu-Beom Jang, Christine Quach, Chengyu Liang
Ultraviolet radiation (UVR)-induced skin pigmentation, afforded by the dark organelles termed melanosomes, accounts for the first-line protection against environmental UVR that increases the risk of developing skin cancers including melanoma. We have recently discovered that UVRAG, originally identified as a BECN1-binding macroautophagy/autophagy protein, appears to have a specialized function in melanosome biogenesis beyond autophagy through its interaction with the biogenesis of lysosome-related organelles complex 1 (BLOC-1)...
September 13, 2018: Autophagy
https://www.readbyqxmd.com/read/30209975/thyroid-hormone-t-3-stimulates-brown-adipose-tissue-activation-via-mitochondrial-biogenesis-and-mtor-mediated-mitophagy
#4
Winifred W Yau, Brijesh K Singh, Ronny Lesmana, Jin Zhou, Rohit A Sinha, Kiraely A Wong, Yajun Wu, Boon-Huat Bay, Shigeki Sugii, Lei Sun, Paul M Yen
The thyroid hormone triiodothyronine (T3 ) activates thermogenesis by uncoupling electron transport from ATP synthesis in brown adipose tissue (BAT) mitochondria. Although T3 can induce thermogenesis by sympathetic innervation, little is known about its cell autonomous effects on BAT mitochondria. We thus examined effects of T3 on mitochondrial activity, autophagy, and metabolism in primary brown adipocytes and BAT and found that T3 increased fatty acid oxidation and mitochondrial respiration as well as autophagic flux, mitophagy, and mitochondrial biogenesis...
September 13, 2018: Autophagy
https://www.readbyqxmd.com/read/30208760/mir223-restrains-autophagy-and-promotes-cns-inflammation-by-targeting-atg16l1
#5
Yan Li, Dongmei Zhou, Yinghui Ren, Zimu Zhang, Xiangdong Guo, MingKun Ma, Zhenyi Xue, Jienv Lv, Hongkun Liu, Qing Xi, Long Jia, Lijuan Zhang, Ying Liu, Qi Zhang, Jun Yan, Yurong Da, Fei Gao, Jianbo Yue, Zhi Yao, Rongxin Zhang
Microglia are innate immune cells in the central nervous system (CNS), that supplies neurons with key factors for executing autophagosomal/lysosomal functions. Macroautophagy/autophagy is a cellular catabolic process that maintains cell balance in response to stress-related stimulation. Abnormal autophagy occurs with many pathologies, such as cancer, and autoimmune and neurodegenerative diseases. Hence, clarification of the mechanisms of autophagy regulation is of utmost importance. Recently, researchers presented microRNAs (miRNAs) as novel and potent modulators of autophagic activity...
September 13, 2018: Autophagy
https://www.readbyqxmd.com/read/30208759/how-does-estrogen-work-on-autophagy
#6
Jin Xiang, Xiang Liu, Jing Ren, Kun Chen, Hong-Lu Wang, Yu-Yang Miao, Miao-Miao Qi
Macroautophagy/autophagy is vital for intracellular quality control and homeostasis. Therefore, careful regulation of autophagy is very important. In the past 10 years, a number of studies have reported that estrogenic effectors affect autophagy. However, some results, especially those regarding the modulatory effect of 17β-estradiol (E2) on autophagy seem inconsistent. Moreover, several clinical trials are already in place combining both autophagy inducers and autophagy inhibitors with endocrine therapies for breast cancer...
September 13, 2018: Autophagy
https://www.readbyqxmd.com/read/30208757/autophagy-regulates-glucose-mediated-root-meristem-activity-by-modulating-ros-production-in-arabidopsis
#7
Li Huang, Lu-Jun Yu, Xue Zhang, Biao Fan, Feng-Zhu Wang, Yang-Shuo Dai, Hua Qi, Ying Zhou, Li-Juan Xie, Shi Xiao
Glucose produced from photosynthesis is a key nutrient signal regulating root meristem activity in plants; however, the underlying mechanisms remain poorly understood. Here, we show that, by modulating reactive oxygen species (ROS) levels, the conserved macroautophagy/autophagy degradation pathway contributes to glucose-regulated root meristem maintenance. In Arabidopsis thaliana roots, a short exposure to elevated glucose temporarily suppresses constitutive autophagosome formation. The autophagy-defective autophagy-related gene (atg) mutants have enhanced tolerance to glucose, established downstream of the glucose sensors, and accumulate less glucose-induced ROS in the root tips...
September 13, 2018: Autophagy
https://www.readbyqxmd.com/read/30208749/histone-methyl-transferases-and-demethylases-in-the-autophagy-regulatory-network-the-emerging-role-of-kdm1a-lsd1-demethylase
#8
Susanna Ambrosio, Andrea Ballabio, Barbara Majello
Macroautophagy/autophagy is a physiological mechanism that is essential for the maintenance of cellular homeostasis and stress adaptation. Defective autophagy is associated with many human diseases, including cancer and neurodegenerative disorders. The emerging implication of epigenetic events in the control of the autophagic process opens new avenues of investigation and offers the opportunity to develop novel therapeutic strategies in diseases associated with dysfunctional autophagy-lysosomal pathways. Accumulating evidence reveals that several methyltransferases and demethylases are essential regulators of autophagy, and recent studies have led to the identification of the lysine demethylase KDM1A/LSD1 as a promising drug target...
September 13, 2018: Autophagy
https://www.readbyqxmd.com/read/30176150/driving-next-generation-autophagy-researchers-towards-translation-drive-an-international-phd-training-program-on-autophagy
#9
Claudine Kraft, Patricia Boya, Patrice Codogno, Zvulun Elazar, Eeva-Liisa Eskelinen, Judith Farrés, Vladimir Kirkin, Heinz Jungbluth, Ana Martinez, Ole Pless, Charlotte Primard, Tassula Proikas-Cezanne, Anne Simonsen, Fulvio Reggiori
The European autophagy consortium Driving next-generation autophagy researchers towards translation (DRIVE) held its kick-off meeting in Groningen on the 14th and 15th of June 2018. This Marie Skłodowska-Curie Early Training Network was approved under the European Union's Horizon 2020 Research and Innovation Program and is funded for 4 years. Within DRIVE, 14 European research teams from academia and industry will train 15 PhD students through applied, cross-disciplinary and collaborative macroautophagy/autophagy research...
September 13, 2018: Autophagy
https://www.readbyqxmd.com/read/30160607/necrotic-apoptotic-and-autophagic-cell-fates-triggered-by-nanoparticles
#10
Reza Mohammadinejad, Mohammad Amin Moosavi, Shima Tavakol, Deniz Özkan Vardar, Asieh Hosseini, Marveh Rahmati, Luciana Dini, Salik Hussain, Ali Mandegary, Daniel J Klionsky
Nanomaterials have gained a rapid increase in use in a variety of applications that pertain to many aspects of human life. The majority of these innovations are centered on medical applications and a range of industrial and environmental uses ranging from electronics to environmental remediation. Despite the advantages of NPs, the knowledge of their toxicological behavior and their interactions with the cellular machinery that determines cell fate is extremely limited. This review is an attempt to summarize and increase our understanding of the mechanistic basis of nanomaterial interactions with the cellular machinery that governs cell fate and activity...
September 13, 2018: Autophagy
https://www.readbyqxmd.com/read/30153072/diverse-mechanisms-of-autophagy-dysregulation-and-their-therapeutic-implications-does-the-shoe-fit
#11
Paalini Sathiyaseelan, Katharina Rothe, Kevin C Yang, Jing Xu, Norman S Chow, Svetlana Bortnik, Courtney Choutka, Cally Ho, Xiaoyan Jiang, Sharon M Gorski
In its third edition, the Vancouver Autophagy Symposium presented a platform for vibrant discussion on the differential roles of macroautophagy/autophagy in disease. This one-day symposium was held at the BC Cancer Research Centre in Vancouver, BC, bringing together experts in cell biology, protein biochemistry and medicinal chemistry across several different disease models and model organisms. The Vancouver Autophagy Symposium featured 2 keynote speakers that are well known for their seminal contributions to autophagy research, Dr...
September 13, 2018: Autophagy
https://www.readbyqxmd.com/read/30145931/pathological-missorting-of-endogenous-mapt-tau-in-neurons-caused-by-failure-of-protein-degradation-systems
#12
Varun Balaji, Senthilvelrajan Kaniyappan, Eckhard Mandelkow, Yipeng Wang, Eva-Maria Mandelkow
Missorting of MAPT/Tau represents one of the early signs of neurodegeneration in Alzheimer disease. The triggers for this are still a matter of debate. Here we investigated the sorting mechanisms of endogenous MAPT in mature primary neurons using microfluidic chambers (MFCs) where cell compartments can be observed separately. Blocking protein degradation pathways with proteasomal or autophagy inhibitors dramatically increased the missorting of MAPT in dendrites on the neuritic side, suggesting that degradation of MAPT in dendrites is a major determinant for the physiological axonal distribution of MAPT...
September 13, 2018: Autophagy
https://www.readbyqxmd.com/read/30081747/zfyve26-spastizin-and-spg11-spatacsin-mutations-in-hereditary-spastic-paraplegia-types-ar-spg15-and-ar-spg11-have-different-effects-on-autophagy-and-endocytosis
#13
Chiara Vantaggiato, Elena Panzeri, Marianna Castelli, Andrea Citterio, Alessia Arnoldi, Filippo Maria Santorelli, Rocco Liguori, Marina Scarlato, Olimpia Musumeci, Antonio Toscano, Emilio Clementi, Maria Teresa Bassi
ZFYVE26/Spastizin and SPG11/Spatacsin encode 2 large proteins that are mutated in hereditary autosomal-recessive spastic paraplegia/paraparesis (HSP) type 15 (AR-SPG15) and type 11 (AR-SPG11), respectively. We previously have reported that AR-SPG15-related ZFYVE26 mutations lead to autophagy defects with accumulation of immature autophagosomes. ZFYVE26 and SPG11 were found to be part of a complex including the AP5 (adaptor related protein complex 5) and to have a critical role in autophagic lysosomal reformation with identification of autophagic and lysosomal defects in cells with both AR-SPG15- and AR-SPG11-related mutations...
September 13, 2018: Autophagy
https://www.readbyqxmd.com/read/30205735/cerkl-regulates-autophagy-via-the-nad-dependent-deacetylase-sirt1
#14
Xuebin Hu, Zhaojing Lu, Shanshan Yu, James Reilly, Fei Liu, Danna Jia, Yayun Qin, Shanshan Han, Xiliang Liu, Zhen Qu, Yuexia Lv, Jingzhen Li, Yuwen Huang, Tao Jiang, Haibo Jia, Qing Wang, Jingyu Liu, Xinhua Shu, Zhaohui Tang, Mugen Liu
Macroautophagy/autophagy is an important intracellular mechanism for the maintenance of cellular homeostasis. Here we show that the CERKL (ceramide kinase like) gene, a retinal degeneration pathogenic gene, plays a critical role in regulating autophagy by stabilizing SIRT1. In vitro and in vivo, suppressing CERKL results in impaired autophagy. SIRT1 is one of the main regulators of acetylation/deacetylation in autophagy. In CERKL-depleted retinas and cells, SIRT1 is downregulated. ATG5 and ATG7, 2 essential components of autophagy, show a higher degree of acetylation in CERKL-depleted cells...
September 12, 2018: Autophagy
https://www.readbyqxmd.com/read/30205729/hmgb1-represses-the-anti-cancer-activity-of-sunitinib-by-governing-tp53-autophagic-degradation-via-its-nucleus-to-cytoplasm-transport
#15
Peihua Luo, Zhifei Xu, Guanqun Li, Hao Yan, Yi Zhu, Hong Zhu, Shenglin Ma, Bo Yang, Qiaojun He
Sunitinib, a multikinase inhibitor approved for a number of cancer indications has a low response rate. Identifying mechanisms of resistance could lead to rational combination regimens that could improve clinical outcomes. Here we report that resistance to sunitinib therapy was driven by autophagic degradation of TP53/p53. Deletion of ATG7 or ATG5 suppressed TP53 degradation, as did knockdown of SQSTM1/p62. Mechanistically, the transport of TP53 from the nucleus to the cytoplasm was essential for the sunitinib-induced autophagic degradation of TP53 and did not require TP53 nuclear export signals (NESs)...
September 11, 2018: Autophagy
https://www.readbyqxmd.com/read/30204036/to-save-or-degrade-balancing-proteasome-homeostasis-to-maximize-cell-survival
#16
Richard S Marshall, Richard D Vierstra
Autophagic degradation of proteasomes (termed proteaphagy) is a conserved mechanism by which cells eliminate excess or damaged particles. This clearance is induced rapidly when organisms are starved for nitrogen and, because proteasomes are highly abundant, their breakdown likely makes an important contribution to the amino acid pools necessary for survival. By contrast, our recent studies found that proteasomes are not degraded in response to carbon starvation, even though bulk macroautophagy is similarly activated...
September 11, 2018: Autophagy
https://www.readbyqxmd.com/read/30153076/transcriptional-and-epigenetic-profiling-of-nutrient-deprived-cells-to-identify-novel-regulators-of-autophagy
#17
J G C Peeters, L W Picavet, S G J M Coenen, M Mauthe, S J Vervoort, E Mocholi, C de Heus, J Klumperman, S J Vastert, F Reggiori, P J Coffer, M Mokry, J van Loosdregt
Macroautophagy (hereafter autophagy) is a lysosomal degradation pathway critical for maintaining cellular homeostasis and viability, and is predominantly regarded as a rapid and dynamic cytoplasmic process. To increase our understanding of the transcriptional and epigenetic events associated with autophagy, we performed extensive genome-wide transcriptomic and epigenomic profiling after nutrient deprivation in human autophagy-proficient and autophagy-deficient cells. We observed that nutrient deprivation leads to the transcriptional induction of numerous autophagy-associated genes...
September 11, 2018: Autophagy
https://www.readbyqxmd.com/read/30176157/capza1-determines-the-risk-of-gastric-carcinogenesis-by-inhibiting-helicobacter-pylori-caga-degraded-autophagy
#18
Hitoshi Tsugawa, Hideki Mori, Juntaro Matsuzaki, Akira Sato, Yoshimasa Saito, Masaya Imoto, Makoto Suematsu, Hidekazu Suzuki
Helicobacter pylori-derived CagA, a type IV secretion system effector, plays a role as an oncogenic driver in gastric epithelial cells. However, upon delivery into gastric epithelial cells, CagA is usually degraded by macroautophagy/autophagy. Hence, the induction of autophagy in H. pylori-infected epithelial cells is an important host-protective ability against gastric carcinogenesis. However, the mechanisms by which autophagosome-lysosome fusion is regulated, are unknown. Here, we report that enhancement of LAMP1 (lysosomal associated membrane protein 1) expression is necessary for autolysosome formation...
September 10, 2018: Autophagy
https://www.readbyqxmd.com/read/30160610/autophagy-mediates-phosphatidylserine-exposure-and-phagosome-degradation-during-apoptosis-through-specific-functions-of-gabarap-lgg-1-and-lc3-lgg-2
#19
Céline Jenzer, Elena Simionato, Céline Largeau, Vincent Scarcelli, Christophe Lefebvre, Renaud Legouis
Phagocytosis and macroautophagy/autophagy are 2 processes involved in lysosome-mediated clearance of extracellular and intracellular components, respectively. Recent studies have identified the recruitment of the autophagic protein LC3 during phagocytosis of apoptotic corpses in what is now called LC3-associated phagocytosis (LAP). LAP is a distinct process from autophagy but it relies on some members of the autophagy pathway to allow efficient degradation of the phagocytosed cargo. We investigated whether both LC3/LGG-2 and GABARAP/LGG-1 are involved in phagocytosis of apoptotic corpses during embryonic development of Caenorhabditis elegans...
September 10, 2018: Autophagy
https://www.readbyqxmd.com/read/30145926/tfeb-driven-endocytosis-coordinates-mtorc1-signaling-and-autophagy
#20
Israel C Nnah, Biao Wang, Chaitali Saqcena, Gregory F Weber, Edward M Bonder, Dustin Bagley, Rossella De Cegli, Gennaro Napolitano, Diego L Medina, Andrea Ballabio, Radek Dobrowolski
The mechanistic target of rapamycin kinase complex 1 (MTORC1) is a central cellular kinase that integrates major signaling pathways, allowing for regulation of anabolic and catabolic processes including macroautophagy/autophagy and lysosomal biogenesis. Essential to these processes is the regulatory activity of TFEB (transcription factor EB). In a regulatory feedback loop modulating transcriptional levels of RRAG/Rag GTPases, TFEB controls MTORC1 tethering to membranes and induction of anabolic processes upon nutrient replenishment...
September 10, 2018: Autophagy
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