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Autophagy

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https://www.readbyqxmd.com/read/27911136/a-functional-nanocarrier-that-copenetrates-extracellular-matrix-and-multiple-layers-of-tumor-cells-for-sequential-and-deep-tumor-autophagy-inhibitor-and-chemotherapeutic-delivery
#1
Yang Wang, Yue Qiu, Sheng Yin, Li Zhang, Kairong Shi, Huile Gao, Zhirong Zhang, Qin He
To further enhance the intensity of deep tumor drug delivery and integrate a combined therapy, we herein report on a core-shell nanocarrier that could simultaneously overcome the double barriers of the extracellular matrix (ECM) and multiple layers of tumor cells (MLTC). A pH-triggered reversible swelling-shrinking core and an MMP2 (matrix metallopeptidase 2) degradable shell were developed to encapsulate chemotherapeutics and macroautophagy/autophagy inhibitors, respectively. MMP2 degraded the shell, which was followed by the autophagy inhibitors release...
December 2, 2016: Autophagy
https://www.readbyqxmd.com/read/27893304/blame-it-on-southern-but-it-s-a-western-blot
#2
Daniel J Klionsky
Edwin M. Southern is a professor emeritus at the University of Oxford. He is perhaps best known for development of the "Southern blot" (Dr. Southern was at the University of Edinburgh when he wrote his landmark paper). The Southern blot provided a scientific breakthrough by allowing scientists to detect a particular DNA sequence without first purifying it from the rest of the genome; the basic method involves the transfer of the DNA to a membrane, followed by detection with a specific probe. Although few people perform Southern blots as originally carried out by Southern, due in part to the more recent technique of the polymerase chain reaction, the basic concept continues to play an important role in molecular biology...
November 28, 2016: Autophagy
https://www.readbyqxmd.com/read/27875098/hlh-30-tfeb-mediated-autophagy-functions-in-a-cell-autonomous-manner-for-epithelium-intrinsic-cellular-defense-against-bacterial-pore-forming-toxin-in-c-elegans
#3
Huan-Da Chen, Cheng-Yuan Kao, Bang-Yu Liu, Shin-Whei Huang, Cheng-Ju Kuo, Jhen-Wei Ruan, Yen-Hung Lin, Cheng-Rung Huang, Yu-Hung Chen, Horng-Dar Wang, Raffi V Aroian, Chang-Shi Chen
Autophagy is an evolutionarily conserved intracellular system that maintains cellular homeostasis by degrading and recycling damaged cellular components. The transcription factor HLH-30/TFEB-mediated autophagy has been reported to regulate tolerance to bacterial infection, but less is known about the bona fide bacterial effector that activates HLH-30 and autophagy. Here, we unveil that bacterial membrane pore-forming toxin (PFT) induces autophagy in an HLH-30-dependent manner in Caenorhabditis elegans. Moreover, autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C...
November 22, 2016: Autophagy
https://www.readbyqxmd.com/read/27875093/autolysosome-biogenesis-and-developmental-senescence-are-regulated-by-both-spns1-and-v-atpase
#4
Tomoyuki Sasaki, Shanshan Lian, Alam Khan, Jesse R Llop, Andrew V Samuelson, Wenbiao Chen, Daniel J Klionsky, Shuji Kishi
Spns1 (Spinster homolog 1 [Drosophila]) in vertebrates, as well as Spin (Spinster) in Drosophila, is a hypothetical lysosomal H(+)-carbohydrate transporter, which functions at a late stage of macroautophagy (hereafter autophagy). The Spin/Spns1 defect induces aberrant autolysosome formation that leads to developmental senescence in the embryonic stage and premature aging symptoms in adulthood. However, the molecular mechanism by which loss of Spin/Spns1 leads to the specific pathogenesis remains to be elucidated...
November 22, 2016: Autophagy
https://www.readbyqxmd.com/read/27875077/march5-rna-promotes-autophagy-migration-and-invasion-of-ovarian-cancer-cells
#5
Jianguo Hu, Ying Meng, Zhanqin Zhang, Qiuting Yan, Xingwei Jiang, Zilan Lv, Lina Hu
MARCH5 is a crucial regulator of mitochondrial fission. However, the expression and function of MARCH5 in ovarian cancer have not been determined. This study investigated the expression and function of MARCH5 in ovarian cancer with respect to its potential role in the tumorigenesis of the disease as well as its usefulness as an early diagnostic marker. We found that the expression of MARCH5 was substantially upregulated in ovarian cancer tissue in comparison with the normal control. Silencing MARCH5 in SKOV3 cells decreased TGFB1-induced cell macroautophagy/autophagy, migration, and invasion in vitro and in vivo, whereas the ectopic expression of MARCH5 in A2780 cells had the opposite effect...
November 22, 2016: Autophagy
https://www.readbyqxmd.com/read/27875067/transiently-expressed-atg16l1-inhibits-autophagosome-biogenesis-and-aberrantly-targets-rab11-positive-recycling-endosomes
#6
Jiehua Li, Zhixia Chen, Michael T Stang, Wentao Gao
The membrane source for autophagosome biogenesis is an unsolved mystery in the study of autophagy. ATG16L1 forms a complex with ATG12-ATG5 (the ATG16L1 complex). The ATG16L1 complex is recruited to autophagic membranes to convert MAP1LC3B-I to MAP1LC3B-II. The ATG16L1 complex dissociates from the phagophore before autophagosome membrane closure. Thus, ATG16L1 can be used as an early event marker for the study of autophagosome biogenesis. We found that among 3 proteins in the ATG16L1 complex, only ATG16L1 formed puncta-like structures when transiently overexpressed...
November 22, 2016: Autophagy
https://www.readbyqxmd.com/read/27846375/ubiquitination-of-ermes-components-by-the-e3-ligase-rsp5-is-involved-in-mitophagy
#7
Naïma Belgareh-Touzé, Laetitia Cavellini, Mickael M Cohen
Mitochondria are dynamic organelles that undergo permanent fission and fusion events. These processes play an essential role in maintaining normal cellular function. In the yeast Saccharomyces cerevisiae, the endoplasmic reticulum-mitochondrial encounter structure (ERMES) is a marker of sites of mitochondrial division, but it is also involved in a plethora of other mitochondrial functions. However, it remains unclear how these different functions are regulated. We show here that Mdm34 and Mdm12, 2 components of ERMES, are ubiquitinated by the E3 ligase Rsp5...
November 15, 2016: Autophagy
https://www.readbyqxmd.com/read/27846374/ubiquitin-coated-nanodiamonds-bind-to-autophagy-receptors-for-entry-into-the-selective-autophagy-pathway
#8
Kuang-Kai Liu, Wei-Ru Qiu, Emmanuel Naveen Raj, Huei-Fang Liu, Hou-Syun Huang, Yu-Wei Lin, Chien-Jen Chang, Ting-Hua Chen, Chinpiao Chen, Huan-Cheng Chang, Jenn-Kang Hwang, Jui-I Chao
Selective macroautophagy/autophagy plays a pivotal role in the processing of foreign pathogens and cellular components to maintain homeostasis in human cells. To date, numerous studies have demonstrated the uptake of nanoparticles by cells, but their intracellular processing through selective autophagy remains unclear. Here we show that carbon-based nanodiamonds (NDs) coated with ubiquitin (Ub) bind to autophagy receptors (SQSTM1 [sequestosome 1], OPTN [optineurin], and CALCOCO2/NDP52 [calcium binding and coiled-coil domain 2]) and are then linked to MAP1LC3/LC3 (microtubule associated protein 1 light chain 3) for entry into the selective autophagy pathway...
November 15, 2016: Autophagy
https://www.readbyqxmd.com/read/27846372/loss-of-ulk1-increases-rps6kb1-ncor1-repression-of-nr1h-lxr-mediated-scd1-transcription-and-augments-lipotoxicity-in-hepatic-cells
#9
Rohit Anthony Sinha, Brijesh K Singh, Jin Zhou, Sherwin Xie, Benjamin L Farah, Ronny Lesmana, Kenji Ohba, Madhulika Tripathi, Sujoy Ghosh, Anthony N Hollenberg, Paul M Yen
Lipotoxicity caused by saturated fatty acids (SFAs) induces tissue damage and inflammation in metabolic disorders. SCD1 (stearoyl-Coenzyme A desaturase 1) converts SFAs to mono-unsaturated fatty acids (MUFAs) that are incorporated into triglycerides and stored in lipid droplets. SCD1 thus helps protect hepatocytes from lipotoxicity and its reduced expression is associated with increased lipotoxic injury in cultured hepatic cells and mouse models. To further understand the role of SCD1 in lipotoxicity, we examined the regulation of Scd1 in hepatic cells treated with palmitate, and found that NR1H/LXR (nuclear receptor subfamily 1 group H) ligand, GW3965, induced Scd1 expression and lipid droplet formation to improve cell survival...
November 15, 2016: Autophagy
https://www.readbyqxmd.com/read/27846365/lysosomal-membrane-protein-sidt2-mediates-the-direct-uptake-of-dna-by-lysosomes
#10
Shu Aizawa, Viorica Raluca Contu, Yuuki Fujiwara, Katsunori Hase, Hisae Kikuchi, Chihana Kabuta, Keiji Wada, Tomohiro Kabuta
Lysosomes degrade macromolecules such as proteins and nucleic acids. We previously identified 2 novel types of autophagy, RNautophagy and DNautophagy, where lysosomes directly take up RNA and DNA, in an ATP-dependent manner, for degradation. We have also reported that SIDT2 (SID1 transmembrane family, member 2), an ortholog of the Caenorhabditis elegans putative RNA transporter SID-1 (systemic RNA interference defective-1), mediates RNA translocation during RNautophagy. In this addendum, we report that SIDT2 also mediates DNA translocation in the process of DNautophagy...
November 15, 2016: Autophagy
https://www.readbyqxmd.com/read/27846364/hsf1-stress-response-pathway-regulates-autophagy-receptor-sqstm1-p62-associated-proteostasis
#11
Yoshihisa Watanabe, Atsushi Tsujimura, Katsutoshi Taguchi, Masaki Tanaka
Proteostasis is important for protecting cells from harmful proteins and is mainly controlled by the HSF1 (heat shock transcription factor 1) stress response pathway. This pathway facilitates protein refolding by molecular chaperones; however, it is unclear whether it functions in autophagy or inclusion formation. The autophagy receptor SQSTM1/p62 is involved in selective autophagic clearance and inclusion formation by harmful proteins, and its phosphorylation at S349, S403, and S407 is required for binding to substrates...
November 15, 2016: Autophagy
https://www.readbyqxmd.com/read/27846363/phospho-ubiquitin-park2-complex-as-a-marker-for-mitophagy-defects
#12
Sylvie Callegari, Silke Oeljeklaus, Bettina Warscheid, Sven Dennerlein, Michael Thumm, Peter Rehling, Jan Dudek
The E3 ubiquitin ligase PARK2 and the mitochondrial protein kinase PINK1 are required for the initiation of mitochondrial damage-induced mitophagy. Together, PARK2 and PINK1 generate a phospho-ubiquitin signal on outer mitochondrial membrane proteins that triggers recruitment of the autophagy machinery. This paper describes the detection of a defined 500-kDa phospho-ubiquitin-rich PARK2 complex that accumulates on mitochondria upon treatment with the membrane uncoupler CCCP. Formation of this complex is dependent on the presence of PINK1 and is absent in mutant forms of PARK2, whereby mitophagy is also arrested...
November 15, 2016: Autophagy
https://www.readbyqxmd.com/read/27813694/autophagy-flux-in-ca1-neurons-of-alzheimer-hippocampus-increased-induction-overburdens-failing-lysosomes-to-propel-neuritic-dystrophy
#13
Matteo Bordi, Martin J Berg, Panaiyur S Mohan, Corrinne M Peterhoff, Melissa J Alldred, Shaoli Che, Stephen D Ginsberg, Ralph A Nixon
Defective autophagy contributes to Alzheimer disease (AD) pathogenesis although evidence is conflicting on whether multiple stages are impaired. Here, for the first time, we have comprehensively evaluated the entire autophagic process specifically in CA1 pyramidal neurons of hippocampus from early and late-stage AD subjects and nondemented controls. CA1 neurons aspirated by laser capture microdissection were analyzed using a custom-designed microarray comprising 578 neuropathology- and neuroscience-associated genes...
November 4, 2016: Autophagy
https://www.readbyqxmd.com/read/27797294/targeting-autophagy-to-overcome-chemoresistance-in-acute-myleogenous-leukemia
#14
Sujan Piya, Michael Andreeff, Gautam Borthakur
Therapeutic inhibition of macroautophagy/autophagy is expected to increase chemosensitivity of cancers and alter tumor-stroma interdependence. The hypoxic, metabolically challenged bone marrow microenvironment confers chemoresistance to leukemia cells. The impact of autophagy inhibition in the context of microenvironment-mediated resistance in leukemia is less explored. Our recent studies demonstrated that co-culture of acute myelogenous leukemia (AML) cells with marrow-derived mesenchymal stromal cells (MSC) induces autophagy in AML cells and increases resistance to genotoxic agents (cytarabine and idarubicin)...
October 31, 2016: Autophagy
https://www.readbyqxmd.com/read/27791533/autophagy-substrate-sqstm1-p62-regulates-chromatin-ubiquitination-during-the-dna-damage-response
#15
Yanan Wang, Wei-Guo Zhu, Ying Zhao
The importance of autophagy in the DNA damage repair process is clear; however, the detailed molecular mechanism is still largely unknown. Here we found that DNA damage-induced histone H2A ubiquitination is suppressed in autophagy-deficient cells in a SQSTM1/p62 dependent manner. SQSTM1 binds and inhibits E3 ligase RNF168s activity, which is essential for H2A ubiquitination. As a result, several important factors for DNA repair cannot be recruited to the sites of DNA double-strand breaks (DSBs) in autophagy-deficient cells, leading to diminished DNA repair and increased sensitivity of cells to radiation...
October 28, 2016: Autophagy
https://www.readbyqxmd.com/read/27791469/new-anti-cancer-molecules-targeting-hspa5-bip-to-induce-endoplasmic-reticulum-stress-autophagy-and-apoptosis
#16
Michaël Cerezo, Stéphane Rocchi
Treatment of melanoma has significantly advanced over the last decade, with the development of targeted therapies against the MAPK pathway and immunotherapies to reactivate antitumor immunity. Unfortunately, currently more than 50% of patients are in treatment failure. Thus, identification of new common cellular vulnerability among melanoma cells is an urgent need and will help in the discovery of more efficient treatments against melanoma. We have focused our study on protein processing and have identified a new compound, HA15, targeting HSPA5/BiP, the master regulator of the unfolded protein response (UPR)...
October 28, 2016: Autophagy
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...
October 28, 2016: Autophagy
https://www.readbyqxmd.com/read/27791467/identification-of-natural-products-with-neuronal-and-metabolic-benefits-through-autophagy-induction
#18
Yuying Fan, Nan Wang, Altea Rocchi, Weiran Zhang, Robert Vassar, Yifa Zhou, Congcong He
Autophagy is a housekeeping lysosomal degradation pathway important for cellular survival, homeostasis and function. Various disease models have shown that upregulation of autophagy may be beneficial to combat disease pathogenesis. However, despite several recently reported small-molecule screens for synthetic autophagy inducers, natural chemicals of diverse structures and functions have not been included in the synthetic libraries, and characterization of their roles in autophagy has been lacking. To discover novel autophagy-regulating compounds and study their therapeutic mechanisms, we used analytic chemistry approaches to isolate natural phytochemicals from a reservoir of medicinal plants used in traditional remedies...
October 28, 2016: Autophagy
https://www.readbyqxmd.com/read/27791464/autophagy-impairment-with-lysosomal-and-mitochondrial-dysfunction-is-an-important-characteristic-of-oxidative-stress-induced-senescence
#19
Haoran Tai, Zhe Wang, Hui Gong, Xiaojuan Han, Jiao Zhou, Xiaobo Wang, Xiawei Wei, Yi Ding, Ning Huang, Jianqiong Qin, Jie Zhang, Shuang Wang, Fei Gao, Zofia M Chrzanowska-Lightowlers, Rong Xiang, Hengyi Xiao
Macroautophagy/autophagy has profound implications for aging. However, the true features of autophagy in the progression of aging remain to be clarified. In the present study, we explored the status of autophagic flux during the development of cell senescence induced by oxidative stress. In this system, although autophagic structures increased, the degradation of SQSTM1/p62 protein, the yellow puncta of mRFP-GFP-LC3 fluorescence and the activity of lysosomal proteolytic enzymes all decreased in senescent cells, indicating impaired autophagic flux with lysosomal dysfunction...
October 28, 2016: Autophagy
https://www.readbyqxmd.com/read/27791458/store-operated-calcium-entry-activated-autophagy-protects-epc-proliferation-via-the-camkk2-mtor-pathway-in-ox-ldl-exposure
#20
Jie Yang, Jie Yu, Dongdong Li, Sanjiu Yu, Jingbin Ke, Lianyou Wang, Yanwei Wang, Youzhu Qiu, Xubin Gao, Jihang Zhang, Lan Huang
Improving biological functions of endothelial progenitor cells (EPCs) is beneficial to maintaining endothelium homeostasis and promoting vascular re-endothelialization. Because macroautophagy/autophagy has been documented as a double-edged sword in cell functions, its effects on EPCs remain to be elucidated. This study was designed to explore the role and molecular mechanisms of store-operated calcium entry (SOCE)-activated autophagy in proliferation of EPCs under hypercholesterolemia. We employed oxidized low-density lipoprotein (ox-LDL) to mimic hypercholesterolemia in bone marrow-derived EPCs from rat...
October 28, 2016: Autophagy
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