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Autophagy

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https://www.readbyqxmd.com/read/28981387/aldh1a1-and-hltf-modulate-the-activity-of-lysosomal-autophagy-inhibitors-in-cancer-cells
#1
Shengfu Piao, Rani Ojha, Vito W Rebecca, Arabinda Samanta, Xiao-Hong Ma, Quentin Mcafee, Michael C Nicastri, Meghan Buckley, Eric Brown, Jeffrey D Winkler, Phyllis A Gimotty, Ravi K Amaravadi
Lysosomal autophagy inhibitors (LAI) such as hydroxychloroquine (HCQ) have significant activity in a subset of cancer cell lines. LAIs are being evaluated in cancer clinical trials, but genetic determinants of sensitivity to LAIs are unknown, making it difficult to predict which tumors would be most susceptible. Here we characterize differentially expressed genes in HCQ-sensitive (-S) and -resistant (-R) cancer cells. Notably, expression of canonical macroautophagy/autophagy genes was not associated with sensitivity to HCQ...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28981380/astrocytes-promote-progression-of-breast-cancer-metastases-to-the-brain-via-a-kiss1-mediated-autophagy
#2
Natalya Kaverina, Anton V Borovjagin, Zaira Kadagidze, Anatoly Baryshnikov, Maria Baryshnikova, Dmitry Malin, Dhimankrishhna Ghosh, Nameeta Shah, Danny R Welch, Patrik Gabikian, Apollon Karseladze, Charles Cobbs, Ilya V Ulasov
Formation of metastases, also known as cancer dissemination, is an important stage of breast cancer (BrCa) development. KISS1 expression is associated with inhibition of metastases development. Recently we have demonstrated that BrCa metastases to the brain exhibit low levels of KISS1 expression at both mRNA and protein levels. By using multicolor immunofluorescence and coculture techniques here we show that normal adult astrocytes in the brain are capable of promoting metastatic transformation of circulating breast cancer cells localized to the brain through secretion of chemokine CXCL12...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28980869/regulation-of-autophagic-lysosome-reformation-by-kinesin-1-clathrin-and-phosphatidylinositol-4-5-bisphosphate
#3
Xu Liu, Daniel J Klionsky
No abstract text is available yet for this article.
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28980867/nrbf2-is-involved-in-the-autophagic-degradation-process-of-app-ctfs-in-alzheimer-disease-models
#4
Chuanbin Yang, Cui-Zan Cai, Ju-Xian Song, Jie-Qiong Tan, Siva Sundara Kumar Durairajan, Ashok Iyaswamy, Ming-Yue Wu, Lei-Lei Chen, Zhenyu Yue, Min Li, Jia-Hong Lu
Alzheimer disease (AD) is the most common neurodegenerative disease characterized by the deposition of amyloid plaque in the brain. The autophagy-associated PIK3C3-containing phosphatidylinositol 3-kinase (PtdIns3K) complex has been shown to interfere with APP metabolism and amyloid beta peptide (Aβ) homeostasis via poorly understood mechanisms. Here we report that NRBF2 (nuclear receptor binding factor 2), a key component and regulator of the PtdIns3K, is involved in APP-CTFs homeostasis in AD cell models...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28980865/morphometric-analysis-of-autophagy-related-structures-in-saccharomyces-cerevisiae
#5
Tatsuya Kawaoka, Shinsuke Ohnuki, Yoshikazu Ohya, Kuninori Suzuki
When macroautophagy (autophagy) is induced by nutrient starvation or rapamycin treatment, Atg (autophagy-related) proteins are assembled at a restricted region close to the vacuole. Subsequently, the phagophore expands to form a closed autophagosome. In Saccharomyces cerevisiae cells overexpressing precursor Ape1 (prApe1), a specific autophagosome cargo protein, the phagophore can be visualized as a cup-shaped structure labeled with green fluorescent protein (GFP)-tagged Atg8. Previously, our group has shown that the maximum length of GFP-Atg8-labeled structures reflects the magnitude of bulk autophagy...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28980860/the-roles-of-intrinsic-disorder-based-liquid-liquid-phase-transitions-in-the-dr-jekyll-mr-hyde-behavior-of-proteins-involved-in-amyotrophic-lateral-sclerosis-and-frontotemporal-lobar-degeneration
#6
Vladimir N Uversky
Pathological developments leading to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are associated with misbehavior of several key proteins, such as SOD1 (superoxide dismutase 1), TARDBP/TDP-43, FUS, C9orf72, and dipeptide repeat proteins generated as a result of the translation of the intronic hexanucleotide expansions in the C9orf72 gene, PFN1 (profilin 1), GLE1 (GLE1, RNA export mediator), PURA (purine rich element binding protein A), FLCN (folliculin), RBM45 (RNA binding motif protein 45), SS18L1/CREST, HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1), HNRNPA2B1 (heterogeneous nuclear ribonucleoprotein A2/B1), ATXN2 (ataxin 2), MAPT (microtubule associated protein tau), and TIA1 (TIA1 cytotoxic granule associated RNA binding protein)...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28980859/ion-channels-in-the-regulation-of-autophagy
#7
Artem Kondratskyi, Kateryna Kondratska, Roman Skryma, Daniel J Klionsky, Natalia Prevarskaya
Autophagy is a cellular process in which the cell degrades and recycles its own constituents. Given the crucial role of autophagy in physiology, deregulation of autophagic machinery is associated with various diseases. Hence, a thorough understanding of autophagy regulatory mechanisms is crucially important for the elaboration of efficient treatments for different diseases. Recently, ion channels, mediating ion fluxes across cellular membranes, have emerged as important regulators of both basal and induced autophagy...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28980858/mitochondria-the-hub-of-energy-deprivation-induced-autophagy
#8
Cong Yi, Jing-Jing Tong, Li Yu
Macroautophagy/autophagy, a process that is highly conserved from yeast to mammals, delivers unwanted cellular contents to lysosomes or the vacuole for degradation. It has been reported that autophagy is crucial for maintaining glucose homeostasis. However, the mechanism by which energy deprivation induces autophagy is not well established. Recently, we found that Mec1/ATR, originally identified as a sensor of DNA damage, is essential for glucose starvation-induced autophagy. Mec1 is recruited to mitochondria where it is phosphorylated by activated Snf1 in response to glucose starvation...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28980855/regulation-of-glycolytic-metabolism-by-autophagy-in-liver-cancer-involves-selective-autophagic-degradation-of-hk2-hexokinase-2
#9
Lin Jiao, Hai-Liang Zhang, Dan-Dan Li, Ke-Li Yang, Jun Tang, Xuan Li, Jiao Ji, Yan Yu, Rui-Yan Wu, Senthilkumar Ravichandran, Jian-Jun Liu, Gong-Kan Feng, Min-Shan Chen, Yi-Xin Zeng, Rong Deng, Xiao-Feng Zhu
Impaired macroautophagy/autophagy and high levels of glycolysis are prevalent in liver cancer. However, it remains unknown whether there is a regulatory relationship between autophagy and glycolytic metabolism. In this study, by utilizing cancer cells with basal or impaired autophagic flux, we demonstrated that glycolytic activity is negatively correlated with autophagy level. The autophagic degradation of HK2 (hexokinase 2), a crucial glycolytic enzyme catalyzing the conversion of glucose to glucose-6-phosphate, was found to be involved in the regulation of glycolysis by autophagy...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28980854/pik3c3-vps34-control-by-acetylation
#10
Hua Su, Wei Liu
PIK3C3/VPS34 (phosphatidylinositol 3-kinase catalytic subunit type 3) converts phosphatidylinositol (PtdIns) to phosphatidylinositol-3-phosphate (PtdIns3P), sustaining macroautophagy/autophagy and endosomal transport. So far, facilitating the assembly of the PIK3C3/VPS34-BECN1-PIK3R4/VPS15/p150 core complex at distinct membranes is the only known way to activate PIK3C3/VPS34 in cells. We have recently revealed a novel mechanism that regulates PIK3C3/VPS34 activation; cellular PIK3C3/VPS34 is repressed under nutrient-rich conditions by EP300/p300-mediated acetylation...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28980850/rilmenidine-promotes-mtor-independent-autophagy-in-the-mutant-sod1-mouse-model-of-amyotrophic-lateral-sclerosis-without-slowing-disease-progression
#11
Nirma D Perera, Rebecca K Sheean, Chew L Lau, Yea Seul Shin, Philip M Beart, Malcolm K Horne, Bradley J Turner
Macroautophagy/autophagy is the main intracellular catabolic pathway in neurons that eliminates misfolded proteins, aggregates and damaged organelles associated with ageing and neurodegeneration. Autophagy is regulated by both MTOR-dependent and -independent pathways. There is increasing evidence that autophagy is compromised in neurodegenerative disorders, which may contribute to cytoplasmic sequestration of aggregation-prone and toxic proteins in neurons. Genetic or pharmacological modulation of autophagy to promote clearance of misfolded proteins may be a promising therapeutic avenue for these disorders...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28976800/conformation-dependent-recognition-of-mutant-htt-huntingtin-proteins-by-selective-autophagy
#12
Xiaoli Sun, Yuhua Fu, Yuyin Pan, Boxun Lu
Protein misfolding is the common theme for neurodegenerative disorders including Huntington's Disease (HD), which is mainly caused by cytotoxicity of the mutant HTT (huntingtin) protein (mHTT). The soluble mHTT has an expanded polyglutamine (polyQ) stretch that may adopt multiple conformations, among which the one recognized by the polyQ antibody 3B5H10 is the most toxic due to unknown mechanisms. In a recent study, we showed that the 3B5H10-recognized mHTT species has a slower degradation rate due to its resistance to selective macroautophagy/autophagy...
October 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28976799/wipi-%C3%AE-propellers-function-as-scaffolds-for-stk11-lkb1-ampk-and-ampk-related-kinase-signaling-in-autophagy
#13
Daniela Bakula, Amelie J Mueller, Tassula Proikas-Cezanne
The article discusses new findings on the role of the 4 human WIPI proteins at the onset of macroautophagy/autophagy. New insights revealing a circuit scaffold function of WIPI β-propellers that interconnect autophagy signaling control with appropriate autophagosome formation are summarized.
October 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28976798/conserved-and-unique-features-of-the-fission-yeast-core-atg1-complex
#14
Tamiza Nanji, Xu Liu, Leon H Chew, Franco K Li, Maitree Biswas, Zhong-Qiu Yu, Shan Lu, Meng-Qiu Dong, Li-Lin Du, Daniel J Klionsky, Calvin K Yip
Although the human ULK complex mediates phagophore initiation similar to the budding yeast Saccharomyces cerevisiae Atg1 complex, this complex contains ATG101 but not Atg29 and Atg31. Here, we analyzed the fission yeast Schizosaccharomyces pombe Atg1 complex, which has a subunit composition that resembles the human ULK complex. Our pairwise coprecipitation experiments showed that while the interactions between Atg1, Atg13, and Atg17 are conserved, Atg101 does not bind Atg17. Instead, Atg101 interacts with the HORMA domain of Atg13 and this enhances the stability of both proteins...
October 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28968134/autophagy-protects-auditory-hair-cells-against-neomycin-induced-damage
#15
Zuhong He, Lingna Guo, Yilai Shu, Qiaojun Fang, Han Zhou, Yongze Liu, Dingding Liu, Ling Lu, Xiaoli Zhang, Xiaoqiong Ding, Dong Liu, Mingliang Tang, Weijia Kong, Suhua Sha, Huawei Li, Xia Gao, Renjie Chai
Aminoglycosides are toxic to sensory hair cells (HCs). Macroautophagy/autophagy is an essential and highly conserved self-digestion pathway that plays important roles in the maintenance of cellular function and viability under stress. However, the role of autophagy in aminoglycoside-induced HC injury is unknown. Here, we first found that autophagy activity was significantly increased, including enhanced autophagosome-lysosome fusion, in both cochlear HCs and HEI-OC-1 cells after neomycin or gentamicin injury, suggesting that autophagy might be correlated with aminoglycoside-induced cell death...
October 2, 2017: Autophagy
https://www.readbyqxmd.com/read/28960115/nbr1-mediated-antiviral-xenophagy-in-plant-immunity
#16
Anders Hafrén, Daniel Hofius
Macroautophagy/autophagy intersects with metazoan virus infections in highly complex and multifaceted ways. Autophagy mechanisms are part of antiviral immunity, but can be manipulated by several viruses to the benefit of infection. In plants, however, the roles of autophagy in virus infections have only recently started to emerge. Here, we present and discuss our recent study that identified 2 prominent functions of autophagy upon cauliflower mosaic virus (CaMV) infection in Arabidopsis. We found that "bulk" autophagy significantly extended the life span of infected plants and increased total virus production...
September 29, 2017: Autophagy
https://www.readbyqxmd.com/read/28949789/lc3s-hire-membrane-breakers-to-attack-viral-shelters
#17
Scott B Biering, Jayoung Choi, Hailey M Brown, Seungmin Hwang
No abstract text is available yet for this article.
September 26, 2017: Autophagy
https://www.readbyqxmd.com/read/28933649/legionella-blocks-autophagy-by-cleaving-stx17-syntaxin-17
#18
Kohei Arasaki, Mitsuo Tagaya
Pathogens subvert host defense systems including autophagy and apoptosis for their survival and proliferation. Legionella pneumophila is a Gram-negative bacterium that grows in alveolar macrophages and causes severe pneumonia. Early during infection Legionella secretes effector proteins that convert the plasma membrane-derived vacuole containing Legionella into an endoplasmic reticulum (ER)-like replicative vacuole. These vacuoles ultimately fuse with the ER, where the pathogen replicates. Recently, we showed that one of the effectors, Lpg1137, is a serine protease that targets the mitochondria-associated ER membrane (MAM) and degrades STX17 (syntaxin 17), a SNARE implicated in macroautophagy/autophagy as well as mitochondria dynamics and membrane trafficking in fed cells...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28933638/autophagy-pathway-cellular-and-molecular-mechanisms
#19
Li Yu, Yang Chen, Sharon A Tooze
Macroautophagy/autophagy is an essential, conserved self-eating process that cells perform to allow degradation of intracellular components, including soluble proteins, aggregated proteins, organelles, macromolecular complexes, and foreign bodies. The process requires formation of a double-membrane structure containing the sequestered cytoplasmic material, the autophagosome, that ultimately fuses with the lysosome. This review will define this process and the cellular pathways required, from the formation of the double membrane to the fusion with lysosomes in molecular terms, and in particular highlight the recent progress in our understanding of this complex process...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28933603/autophagy-enables-retromer-dependent-plasma-membrane-translocation-of-slc2a1-glut1-to-enhance-glucose-uptake
#20
Srirupa Roy, Jayanta Debnath
No abstract text is available yet for this article.
September 21, 2017: Autophagy
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