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Autophagy

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https://www.readbyqxmd.com/read/29215322/aberrant-sirt6-expression-contributes-to-melanoma-growth-role-of-the-autophagy-paradox-and-igf-akt-signaling
#1
Liwen Wang, Weinan Guo, Jinyuan Ma, Wei Dai, Lin Liu, Sen Guo, Jiaxi Chen, Huina Wang, Yuqi Yang, Xiuli Yi, Gang Wang, Tianwen Gao, Guannan Zhu, Chunying Li
Melanoma is among the most life-threatening cancer. The pathogenesis of melanoma has not been fully elucidated. Recently, dysregulated macroautophagy/autophagy has been found to play a critical but inconsistent role in modulating melanoma growth at different stages, with the regulatory mechanism unclear. The histone deacetylase SIRT6 (sirtuin 6) is a known autophagy regulator, and its involvement in cancer development has been reported. Therefore, we sought to determine the role of SIRT6 in melanoma growth and detect its possible link with autophagy in the current study...
December 7, 2017: Autophagy
https://www.readbyqxmd.com/read/29198173/autophagy-inhibition-promotes-snca-alpha-synuclein-release-and-transfer-via-extracellular-vesicles-with-a-hybrid-autophagosome-exosome-like-phenotype
#2
Georgia Minakaki, Stefanie Menges, Agnes Kittel, Evangelia Emmanouilidou, Iris Schaeffner, Katalin Barkovits, Anna Bergmann, Edward Rockenstein, Anthony Adame, Franz Marxreiter, Brit Mollenhauer, Douglas Galasko, Edit Irén Buzás, Ursula Schlötzer-Schrehardt, Katrin Marcus, Wei Xiang, Dieter Chichung Lie, Kostas Vekrellis, Eliezer Masliah, Jürgen Winkler, Jochen Klucken
The autophagy-lysosome pathway (ALP) regulates intracellular homeostasis of the cytosolic protein SNCA/alpha-synuclein and is impaired in synucleinopathies, including Parkinson disease and dementia with Lewy bodies (DLB). Emerging evidence suggests that ALP influences SNCA release, but the underlying cellular mechanisms are not well understood. Several studies identified SNCA in exosome/extracellular vesicle (EV) fractions. EVs are generated in the multivesicular body compartment and either released upon its fusion with the plasma membrane, or cleared via the ALP...
December 4, 2017: Autophagy
https://www.readbyqxmd.com/read/29198169/stress-response-transcription-factors-msn2-and-msn4-couple-torc2-ypk1-signaling-and-mitochondrial-respiration-to-atg8-gene-expression-and-autophagy
#3
Ariadne Vlahakis, Nerea Lopez Muniozguren, Ted Powers
Macroautophagy/autophagy is a starvation and stress-induced catabolic process critical for cellular homeostasis and adaptation. Several Atg proteins are involved in the formation of the autophagosome and subsequent degradation of cytoplasmic components, a process termed autophagy flux. Additionally, the expression of several Atg proteins, in particular Atg8, is modulated transcriptionally, yet the regulatory mechanisms involved remain poorly understood. Here we demonstrate that the AGC kinase Ypk1, target of the rapamycin-insensitive TORC2 signaling pathway, controls ATG8 expression by repressing the heterodimeric Zinc-finger transcription factors Msn2 and Msn4...
December 4, 2017: Autophagy
https://www.readbyqxmd.com/read/29173006/systematic-analysis-of-atg13-domain-requirements-for-autophagy-induction
#4
Nora Wallot-Hieke, Neha Verma, David Schlütermann, Niklas Berleth, Jana Deitersen, Philip Böhler, Fabian Stuhldreier, Wenxian Wu, Sabine Seggewiß, Christoph Peter, Holger Gohlke, Noboru Mizushima, Björn Stork
Macroautophagy/autophagy is an evolutionarily conserved cellular process whose induction is regulated by the ULK1 protein kinase complex. The subunit ATG13 functions as an adaptor protein by recruiting ULK1, RB1CC1 and ATG101 to a core ULK1 complex. Furthermore, ATG13 directly binds both phospholipids and members of the Atg8 family. The central involvement of ATG13 in complex formation makes it an attractive target for autophagy regulation. Here, we analyzed known interactions of ATG13 with proteins and lipids for their potential modulation of ULK1 complex formation and autophagy induction...
November 26, 2017: Autophagy
https://www.readbyqxmd.com/read/29172997/identification-of-anxa2-annexin-a2-as-a-specific-bleomycin-target-to-induce-pulmonary-fibrosis-by-impeding-tfeb-mediated-autophagic-flux
#5
Kui Wang, Tao Zhang, Yunlong Lei, Xuefeng Li, Jingwen Jiang, Jiang Lan, Yuan Liu, Haining Chen, Wei Gao, Na Xie, Qiang Chen, Xiaofeng Zhu, Xiang Liu, Ke Xie, Yong Peng, Edouard C Nice, Min Wu, Canhua Huang, Yuquan Wei
Bleomycin is a clinically potent anticancer drug used for the treatment of germ-cell tumors, lymphomas and squamous-cell carcinomas. Unfortunately, the therapeutic efficacy of bleomycin is severely hampered by the development of pulmonary fibrosis. However, the mechanisms underlying bleomycin-induced pulmonary fibrosis, particularly the molecular target of bleomycin, remains unknown. Here, using a chemical proteomics approach, we identify ANXA2 (annexin A2) as a direct binding target of bleomycin. The interaction of bleomycin with ANXA2 was corroborated both in vitro and in vivo...
November 26, 2017: Autophagy
https://www.readbyqxmd.com/read/29172924/pink1-prkn-park2-pathway-of-mitophagy-is-activated-to-protect-against-renal-ischemia-reperfusion-injury
#6
Chengyuan Tang, Hailong Han, Mingjuan Yan, Shiyao Zhu, Jing Liu, Zhiwen Liu, Liyu He, Jieqiong Tan, Yu Liu, Hong Liu, Lin Sun, Shaobin Duan, Youming Peng, Fuyou Liu, Xiao-Ming Yin, Zhuohua Zhang, Zheng Dong
Damaged or dysfunctional mitochondria are toxic to the cell by producing reactive oxygen species and releasing cell death factors. Therefore, timely removal of these organelles is critical to cellular homeostasis and viability. Mitophagy is the mechanism of selective degradation of mitochondria via autophagy. The significance of mitophagy in kidney diseases, including ischemic acute kidney injury (AKI), has yet to be established, and the involved pathway of mitophagy remains poorly understood. Here, we show that mitophagy is induced in renal proximal tubular cells in both in vitro and in vivo models of ischemic AKI...
November 26, 2017: Autophagy
https://www.readbyqxmd.com/read/29171784/necroptosis-promotes-autophagy-dependent-upregulation-of-damp-and-results-in-immunosurveillance
#7
Sheng-Yen Lin, Sung-Yuan Hsieh, Yi-Ting Fan, Wen-Chi Wei, Pei-Wen Hsiao, Dai-Hua Tsai, Tzong-Shoon Wu, Ning-Sun Yang
Programmed necrosis, necroptosis, is considered to be a highly immunogenic activity, often mediated via the release of damage-associated molecular patterns (DAMPs). Interestingly, enhanced macroautophagic/autophagic activity is often found to be accompanied by necroptosis. However, the possible role of autophagy in the immunogenicity of necroptotic death remains largely obscure. In this study, we investigated the possible mechanistic correlation between phytochemical shikonin-induced autophagy and the shikonin-induced necroptosis for tumor immunogenicity...
November 24, 2017: Autophagy
https://www.readbyqxmd.com/read/29166823/foot-and-mouth-disease-virus-capsid-protein-vp2-activates-the-cellular-eif2s1-atf4-pathway-and-induces-autophagy-via-hspb1
#8
Peng Sun, Shumin Zhang, Xiaodong Qin, Xingni Chang, Xiaorui Cui, Haitao Li, Shuaijun Zhang, Huanghuang Gao, Penghua Wang, Zhidong Zhang, Jianxun Luo
Foot-and-mouth disease virus (FMDV) can result in economical destruction of cloven-hoofed animals. FMDV infection has been reported to induce macroautophagy/autophagy; however, the precise molecular mechanisms of autophagy induction and effect of FMDV capsid protein on autophagy remain unknown. In the present study, we report that FMDV infection induced a complete autophagy process in the natural host cells of FMDV, and inhibition of autophagy significantly decreased FMDV production, suggesting that FMDV-induced autophagy facilitates viral replication...
November 23, 2017: Autophagy
https://www.readbyqxmd.com/read/29165043/autophagy-balances-inflammation-in-innate-immunity
#9
Vojo Deretic, Beth Levine
Macroautophagy/autophagy is a homeostatic process with multiple effects on immunity. One of the pivotal contributions of autophagy in immunity is the cell autonomous control of inflammation. This property leads to systemic consequences and thereby influences the development of innate and adaptive immunity, which promotes or suppresses pathology in various disease contexts. In this review we focus on the intersections between autophagy and inflammasome activation, autophagy and interferons, and autophagy and inflammation in association with infection...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29165042/suppressed-translation-as-a-mechanism-of-initiation-of-casp8-caspase-8-dependent-apoptosis-in-autophagy-deficient-nsclc-cells-under-nutrient-limitation
#10
Giulia Allavena, Francesca Cuomo, Georg Baumgartner, Tadeja Bele, Alexander Yarar Sellgren, Kyaw Soe Oo, Kaylee Johnson, Vladimir Gogvadze, Boris Zhivotovsky, Vitaliy O Kaminskyy
Macroautophagy/autophagy inhibition under stress conditions is often associated with increased cell death. We found that under nutrient limitation, activation of CASP8/caspase-8 was significantly increased in autophagy-deficient lung cancer cells, which precedes mitochondria outer membrane permeabilization (MOMP), CYCS/cytochrome c release, and activation of CASP9/caspase-9, indicating that under such conditions the activation of CASP8 is a primary event in the initiation of apoptosis as well as essential to reduce clonogenic survival of autophagy-deficient cells...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29165041/akt-mediated-phosphorylation-of-atg4b-impairs-mitochondrial-activity-and-enhances-the-warburg-effect-in-hepatocellular-carcinoma-cells
#11
Zhenhong Ni, Jintao He, Yaran Wu, Changjiang Hu, Xufang Dai, Xiaojing Yan, Bo Li, Xinzhe Li, Haojun Xiong, Yuming Li, Song Li, Liang Xu, Yongsheng Li, Jiqin Lian, Fengtian He
Phosphorylation is a major type of post-translational modification, which can influence the cellular physiological function. ATG4B, a key macroautophagy/autophagy-related protein, has a potential effect on the survival of tumor cells. However, it is still unknown as to the role of ATG4B phosphorylation in cancers. In this study, we identified a novel phosphorylation site at Ser34 of ATG4B induced by AKT in HCC cells. The phosphorylation of ATG4B at Ser34 had little effect on autophagic flux, but promoted the Warburg effect including the increase of L-lactate production and glucose consumption, and the decrease of oxygen consumption in HCC cells...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29165031/bst2-inhibits-type-i-ifn-interferon-signaling-by-accelerating-mavs-degradation-through-calcoco2-directed-autophagy
#12
Shouheng Jin, Jun Cui
Macroautophagy/autophagy is a conserved lysosomal degradation system that breaks down intracellular material through the formation of double-membrane autophagosomes in eukaryotic cells. Cargo receptors have been illustrated to play essential roles in capturing and delivering specific substrates into phagophores, the precursors to autophagosomes, for degradation. However, the detailed mechanism underlying selective recognition of the substrates for autophagic degradation remains poorly understood. Recently, we have revealed that IFN (interferon)-induced BST2 recruits the E3 ubiquitin ligase MARCH8 to catalyze the K27-linked ubiquitination of MAVS for CALCOCO2-directed autophagic degradation, hence inhibiting DDX58-mediated type I interferon signaling through a negative feedback loop...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29165030/in-mammalian-skeletal-muscle-phosphorylation-of-tomm22-by-protein-kinase-csnk2-ck2-controls-mitophagy
#13
Bojana Kravic, Angelika B Harbauer, Vanina Romanello, Luca Simeone, F-Nora Vögtle, Tobias Kaiser, Marion Straubinger, Danyil Huraskin, Martin Böttcher, Cristina Cerqua, Eva Denise Martin, Daniel Poveda-Huertes, Andreas Buttgereit, Adam J Rabalski, Dieter Heuss, Rüdiger Rudolf, Oliver Friedrich, David Litchfield, Michael Marber, Leonardo Salviati, Dimitrios Mougiakakos, Winfried Neuhuber, Marco Sandri, Chris Meisinger, Said Hashemolhosseini
In yeast, Tom22 the central component of the TOMM (translocase of outer mitochondrial membrane) receptor complex is responsible for the recognition and translocation of synthesized mitochondrial precursor proteins, and its protein kinase CK2-dependent phosphorylation is mandatory for TOMM complex biogenesis and proper mitochondrial protein import. In mammals, the biological function of protein kinase CSNK2/CK2 remains vastly elusive and it is unknown whether CSNK2-dependent phosphorylation of TOMM protein subunits has a similar role as that in yeast...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29164996/cptp-a-sphingolipid-transfer-protein-that-regulates-autophagy-and-inflammasome-activation
#14
Shrawan Kumar Mishra, Yong-Guang Gao, Yibin Deng, Charles E Chalfant, Edward H Hinchcliffe, Rhoderick E Brown
The macroautophagy/autophagy and inflammasome pathways are linked through their roles in innate immunity and chronic inflammatory disease. Ceramide-1-phosphate (C1P) is a bioactive sphingolipid that regulates pro-inflammatory eicosanoid production. Whether C1P also regulates autophagy and inflammasome assembly/activation is not known. Here we show that CPTP (a protein that traffics C1P from its site of phosphorylation in the trans-Golgi to target membranes) regulates both autophagy and inflammasome activation...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29164995/novel-polyubiquitin-imaging-system-polyub-fc-reveals-that-k33-linked-polyubiquitin-is-recruited-by-sqstm1-p62
#15
Yoichi Nibe, Shigeru Oshima, Masanori Kobayashi, Chiaki Maeyashiki, Yu Matsuzawa, Kana Otsubo, Hiroki Matsuda, Emi Aonuma, Yasuhiro Nemoto, Takashi Nagaishi, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Shinichiro Nakada, Mamoru Watanabe
Ubiquitin chains are formed with 8 structurally and functionally distinct polymers. However, the functions of each polyubiquitin remain poorly understood. We developed a polyubiquitin-mediated fluorescence complementation (PolyUb-FC) assay using Kusabira Green (KG) as a split fluorescent protein. The PolyUb-FC assay has the advantage that monoubiquitination is nonfluorescent and chain-specific poly-ubiquitination can be directly visualized in living cells without using antibodies. We applied the PolyUb-FC assay to examine K33-linked polyubiquitin...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29160747/lipopolysaccharide-mediates-hepatic-stellate-cell-activation-by-regulating-autophagy-and-retinoic-acid-signaling
#16
Ming Chen, Jiaxing Liu, Wenqi Yang, Wenhua Ling
Bacterial translocation and lipopolysaccharide (LPS) leakage occur at a very early stage of liver fibrosis in animal models. We studied the role of LPS in hepatic stellate cell (HSC) activation and the underlying mechanisms in vitro and in vivo. Herein, we demonstrated that LPS treatment led to a dramatic increase in autophagosome formation and autophagic flux in LX-2 cells and HSCs, which was mediated through the AKT-MTOR and AMPK-ULK1 pathway. LPS significantly decreased the lipid content, including the lipid droplet (LD) number and lipid staining area in HSCs; pretreatment with macroautophagy/autophagy inhibitors or silencing ATG5 attenuated this decrease...
November 21, 2017: Autophagy
https://www.readbyqxmd.com/read/29157095/endothelial-autophagic-flux-hampers-atherosclerotic-lesion-development
#17
Marouane Kheloufi, Anne-Clemence Vion, Adel Hammoutene, Johanne Poisson, Juliette Lasselin, Cecile Devue, Isabelle Pic, Nicolas Dupont, Johanna Busse, Konstantin Stark, Julie Lafaurie-Janvore, Abdul I Barakat, Xavier Loyer, Michele Souyri, Benoit Viollet, Pierre Julia, Alain Tedgui, Patrice Codogno, Chantal M Boulanger, Pierre-Emmanuel Rautou
Blood flowing in arteries generates shear forces at the surface of the vascular endothelium that control its anti-atherogenic properties. However, due to the architecture of the vascular tree, these shear forces are heterogeneous and atherosclerotic plaques develop preferentially in areas where shear is low or disturbed. Here we review our recent study showing that elevated shear forces stimulate endothelial autophagic flux and that inactivating the endothelial macroautophagy/autophagy pathway promotes a pro-inflammatory, pro-senescent and pro-apoptotic cell phenotype despite the presence of atheroprotective shear forces...
November 20, 2017: Autophagy
https://www.readbyqxmd.com/read/29157087/thanatos-an-integrative-data-resource-of-proteins-and-post-translational-modifications-in-the-regulation-of-autophagy
#18
Wankun Deng, Lili Ma, Ying Zhang, Jiaqi Zhou, Yongbo Wang, Zexian Liu, Yu Xue
Macroautophagy/autophagy is a highly conserved process for degrading cytoplasmic contents, determines cell survival or death, and regulates the cellular homeostasis. Besides ATG proteins, numerous regulators together with various post-translational modifications (PTMs) are also involved in autophagy. In this work, we collected 4,237 experimentally identified proteins regulated in autophagy and cell death pathways from the literature. Then we computationally identified potential orthologs of known proteins, and developed a comprehensive database of The Autophagy, Necrosis, ApopTosis OrchestratorS (THANATOS, http://thanatos...
November 20, 2017: Autophagy
https://www.readbyqxmd.com/read/29157081/regulation-of-becn1-mediated-autophagy-by-hspb6-insights-from-a-human-hspb6-s10f-mutant
#19
Guan-Sheng Liu, Hongyan Zhu, Wen-Feng Cai, Xiaohong Wang, Min Jiang, Kobina Essandoh, Elizabeth Vafiadaki, Kobra Haghighi, Chi Keung Lam, George Gardner, George Adly, Persoulla Nicolaou, Despina Sanoudou, Qiangrong Liang, Jack Rubinstein, Guo-Chang Fan, Evangelia G Kranias
HSPB6/Hsp20 (heat shock protein family B [small] member 6) has emerged as a novel cardioprotector against stress-induced injury. We identified a human mutant of HSPB6 (HSPB6(S10F)) exclusively present in dilated cardiomyopathy (DCM) patients. Cardiac expression of this mutant in mouse hearts resulted in remodeling and dysfunction, which progressed to heart failure and early death. These detrimental effects were associated with reduced interaction of mutant HSPB6(S10F) with BECN1/Beclin 1, leading to BECN1 ubiquitination and its proteosomal degradation...
November 20, 2017: Autophagy
https://www.readbyqxmd.com/read/29157080/secretory-autophagy-holds-the-key-to-lysozyme-secretion-during-bacterial-infection-of-the-intestine
#20
Elizabeth Delorme-Axford, Daniel J Klionsky
In 2013, Dr. Lora Hooper and colleagues described the induction of antibacterial macroautophagy/autophagy in intestinal epithelial cells as a cytoprotective host defense mechanism against invading Salmonella enterica serovar Typhimurium (S. Typhimurium). Canonical autophagy functions in a primarily degradative capacity to safeguard cells and ensure survival during stress conditions, including pathogen infection. In contrast, secretory autophagy has emerged as an alternative nondegradative mechanism for cellular trafficking and unconventional protein secretion...
November 20, 2017: Autophagy
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