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https://www.readbyqxmd.com/read/28343064/a-barley-homolog-of-yeast-atg6-is-involved-in-multiple-abiotic-stress-responses-and-stress-resistance-regulation
#1
Xiaowei Zeng, Zhanghui Zeng, Cuicui Liu, Weiyi Yuan, Ning Hou, Hongwu Bian, Muyuan Zhu, Ning Han
Autophagy is a highly conserved degradation pathway among eukaryote cells, which can recycle damaged or unwanted cell materials upon encountering stress conditions. As a key component of the Class III PI3K kinase complex, ATG6/Beclin-1 is essential for autophagosome formation. In this study, we isolated a putative HvATG6 gene in barley genome. The protein encoded by HvATG6 shares high sequence identity to ATG6 orthologs in rice and wheat, and has a typical autophagy-specific domain containing segments of repeated β-sheet-α-helix...
March 19, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28342982/mastocarcinoma-therapy-synergistically-promoted-by-lysosome-dependent-apoptosis-specifically-evoked-by-5-fu-nanogel-system-with-passive-targeting-and-ph-activatable-dual-function
#2
Xiandi Zhu, Yn Sun, Di Chen, Jingfeng Li, Xia Dong, Jie Wang, Huaiwen Chen, Ying Wang, Fulei Zhang, Jinaxin Dai, Rogério P Pirraco, Shangjing Guo, Alexandra P Marques, Rui L Reis, Wei Li
This manuscript describes a synergistic therapy for mastocarcinoma by pH and temperature dual-sensitive nanogel, and effects of microstructure, composition and properties of nanogel on the cellular response mechanism. The extracellular internalization of nanogels was obviously enhanced, due to the passive targeting function at T>VPTT. Interestingly, the increased cytotoxicity was further synergistically enhanced by an unexpected apoptosis as evoked by the 5-fluorouracil loaded nanogel (FLNG). The systemically evaluation of the effectors generated from different sub-cellular organelles including endosome, lysosome, autophagosome confirmed that it was a lysomal dependent apoptosis...
March 22, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28339018/role-of-autophagy-in-the-progression-of-osteoarthritis-the-autophagy-inhibitor-3-methyladenine-aggravates-the-severity-of-experimental-osteoarthritis
#3
Ni-Tao Cheng, Hai Meng, Li-Feng Ma, Liang Zhang, Hao-Miao Yu, Zhen-Zhong Wang, Ai Guo
Accumulating evidence suggests that autophagy is closely related to the pathogenesis of osteoarthritis (OA). The aim of this study was to determine the changes in autophagy during the progression of OA and to elucidate the specific role of autophagy in OA. For this purpose, a cellular model of OA was generated by stimulating SW1353 cells with interleukin (IL)-1β and a rabbit model of OA was also established by an intra-articular injection of collagenase, followed by treatment with the autophagy specific inhibitor, 3-methyladenine (3-MA)...
March 23, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28331162/carbon-and-nitrogen-depletion-induced-nucleophagy-and-selective-autophagic-sequestration-of-a-whole-nucleus-in-multinucleate-cells-of-the-filamentous-fungus-aspergillus-oryzae
#4
Takashi Kikuma, Takahiro Mitani, Takahiro Kohara, Jun-Ichi Maruyama, Katsuhiko Kitamoto
Autophagy is a conserved cellular degradation process in eukaryotes, in which cytoplasmic components and organelles are digested in vacuoles/lysosomes. Recently, autophagic degradation of nuclear materials, termed "nucleophagy", has been reported. In the multinucleate filamentous fungus Aspergillus oryzae, a whole nucleus is degraded by nucleophagy after prolonged culture. While developing an H2B-EGFP processing assay for the evaluation of nucleophagy in A. oryzae, we found that nucleophagy is efficiently induced by carbon or nitrogen depletion...
March 22, 2017: Journal of General and Applied Microbiology
https://www.readbyqxmd.com/read/28331029/the-sac1-domain-in-synaptojanin-is-required-for%C3%A2-autophagosome-maturation-at-presynaptic%C3%A2-terminals
#5
Roeland Vanhauwaert, Sabine Kuenen, Roy Masius, Adekunle Bademosi, Julia Manetsberger, Nils Schoovaerts, Laura Bounti, Serguei Gontcharenko, Jef Swerts, Sven Vilain, Marina Picillo, Paolo Barone, Shashini T Munshi, Femke Ms de Vrij, Steven A Kushner, Natalia V Gounko, Wim Mandemakers, Vincenzo Bonifati, Frederic A Meunier, Sandra-Fausia Soukup, Patrik Verstreken
Presynaptic terminals are metabolically active and accrue damage through continuous vesicle cycling. How synapses locally regulate protein homeostasis is poorly understood. We show that the presynaptic lipid phosphatase synaptojanin is required for macroautophagy, and this role is inhibited by the Parkinson's disease mutation R258Q. Synaptojanin drives synaptic endocytosis by dephosphorylating PI(4,5)P2, but this function appears normal in Synaptojanin(RQ) knock-in flies. Instead, R258Q affects the synaptojanin SAC1 domain that dephosphorylates PI(3)P and PI(3,5)P2, two lipids found in autophagosomal membranes...
March 22, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28330855/conserved-atg8-recognition-sites-mediate-atg4-association-with-autophagosomal-membranes-and-atg8-deconjugation
#6
Susana Abreu, Franziska Kriegenburg, Rubén Gómez-Sánchez, Muriel Mari, Jana Sánchez-Wandelmer, Mads Skytte Rasmussen, Rodrigo Soares Guimarães, Bettina Zens, Martina Schuschnig, Ralph Hardenberg, Matthias Peter, Terje Johansen, Claudine Kraft, Sascha Martens, Fulvio Reggiori
Deconjugation of the Atg8/LC3 protein family members from phosphatidylethanolamine (PE) by Atg4 proteases is essential for autophagy progression, but how this event is regulated remains to be understood. Here, we show that yeast Atg4 is recruited onto autophagosomal membranes by direct binding to Atg8 via two evolutionarily conserved Atg8 recognition sites, a classical LC3-interacting region (LIR) at the C-terminus of the protein and a novel motif at the N-terminus. Although both sites are important for Atg4-Atg8 interaction in vivo, only the new N-terminal motif, close to the catalytic center, plays a key role in Atg4 recruitment to autophagosomal membranes and specific Atg8 deconjugation...
March 22, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28324488/flow-cytometer-monitoring-of-bnip3-and-bnip3l-nix-dependent-mitophagy
#7
Matilda Šprung, Ivan Dikic, Ivana Novak
Mitochondria are organelles with numerous vital roles in cellular metabolism. Impaired or damaged mitochondria are degraded in autophagolysosomes in a process known as mitophagy. Given the fundamental role of mitophagy in maintenance of cellular homeostasis, methods and techniques with which to study this process are constantly evolving and emerging. So far, mitophagy flux was mostly monitored using fluorescently labeled LC3 protein on autophagosomal membrane and any of the labeled outer mitochondrial membrane proteins...
March 22, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28323964/dysregulated-autophagy-in-hepatocytes-promotes-bisphenol-a-bpa-induced-hepatic-lipid-accumulation-in-male-mice
#8
Shumin Yang, Ting Li, Aipin Zhang, Rufei Gao, Chuan Peng, Lulu Liu, Qingfeng Cheng, Mei Mei, Ying Song, Xiaojiao Xiang, Chaodong Wu, Xiaoqiu Xiao, Qifu Li
Context: Accumulating evidence suggests that bisphenol A (BPA) exposure is associated with nonalcoholic fatty liver disease. Disruption of autophagy causes lipid accumulation in hepatocytes. Whether and how BPA regulates autophagy remains to be explored. Objective: We investigated the effect of BPA on autophagy in hepatocytes and examined the influence of BPA-regulated autophagy on hepatic lipid accumulation. Design: Male CD1 mice were treated with BPA for eight weeks, followed by histological and biochemical evaluation of liver lipids and autophagy...
February 21, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323521/hs1bp3-provides-a-novel-mechanism-of-negative-autophagy-regulation-through-membrane-lipids
#9
Zhangyuan Yin, Daniel J Klionsky
The formation and maturation of the autophagosome, a morphological hallmark of macroautophagy/autophagy, is tightly controlled with regard to location, timing and intensity. Various proteins have been characterized to be essential in regulating autophagosome biogenesis, whereas little is known about the roles of specific lipids and their metabolizing enzymes in this process. In a recent paper, Holland et al. identified the phosphoinositide-binding protein HS1BP3 as a novel negative regulator of autophagosome formation...
March 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28322865/palmitic-acid-elicits-hepatic-stellate-cell-activation-through-inflammasomes-and-hedgehog-signaling
#10
Na-Na Duan, Xue-Jing Liu, Jian Wu
AIMS: Activation of hepatic stellate cells (HSCs) plays a pivotal role at the center of the fibrogenic progression in nonalcoholic steatohepatitis (NASH). However, it is poorly understood that how various molecules interact within HSCs during the progression of NASH to fibrosis. The aim of the present study is to delineate how inflammasome molecules, hedgehog signaling and autophagy provoke HSC activation using palmitic acid (PA) as a major insult. MAIN METHODS: Inflammasome activation, hedgehog signaling activity and autophagy in PA-exposed HSCs were determined to investigate their role in activation of human and rodent HSC lines or primary HSCs...
March 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28322744/basal-ryanodine-receptor-activity-suppresses-autophagic-flux
#11
Tim Vervliet, Isabel Pintelon, Kirsten Welkenhuyzen, Martin D Bootman, Hiroko Bannai, Katsuhiko Mikoshiba, Wim Martinet, Nael Nadif Kasri, Jan B Parys, Geert Bultynck
The inositol 1,4,5-trisphosphate receptors (IP3Rs) and intracellular Ca(2+) signaling are critically involved in regulating different steps of autophagy, a lysosomal degradation pathway. The ryanodine receptors (RyR), intracellular Ca(2+)-release channels mainly expressed in excitable cell types including muscle and neurons, have however not yet been extensively studied in relation to autophagy. Yet, aberrant expression and excessive activity of RyRs in these tissues has been implicated in the onset of several diseases including Alzheimer's disease, where impaired autophagy regulation contributes to the pathology...
March 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28321485/initial-autophagic-protection-switches-to-disruption-of-autophagic-flux-by-lysosomal-instability-during-cadmium-stress-accrual-in-renal-nrk-52e-cells
#12
W-K Lee, S Probst, M P Santoyo-Sánchez, W Al-Hamdani, I Diebels, J-K von Sivers, E Kerek, E J Prenner, F Thévenod
The renal proximal tubule (PT) is the major target of cadmium (Cd(2+)) toxicity where Cd(2+) causes stress and apoptosis. Autophagy is induced by cell stress, e.g., endoplasmic reticulum (ER) stress, and may contribute to cell survival or death. The role of autophagy in Cd(2+)-induced nephrotoxicity remains unsettled due to contradictory results and lack of evidence for autophagic machinery damage by Cd(2+). Cd(2+)-induced autophagy in rat kidney PT cell line NRK-52E and its role in cell death was investigated...
March 20, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28320970/borc-kinesin-1-ensemble-drives-polarized-transport-of-lysosomes-into-the-axon
#13
Ginny G Farías, Carlos M Guardia, Raffaella De Pace, Dylan J Britt, Juan S Bonifacino
The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly understood. Here we show that an ensemble of BORC, Arl8, SKIP, and kinesin-1, previously shown to mediate centrifugal transport of lysosomes in nonneuronal cells, specifically drives lysosome transport into the axon, and not the dendrites, in cultured rat hippocampal neurons...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320742/development-of-lc3-gabarap-sensors-containing-a-lir-and-a-hydrophobic-domain-to-monitor-autophagy
#14
You-Kyung Lee, Yong-Woo Jun, Ha-Eun Choi, Yang Hoon Huh, Bong-Kiun Kaang, Deok-Jin Jang, Jin-A Lee
Macroautophagy allows for bulk degradation of cytosolic components in lysosomes. Overexpression of GFP/RFP-LC3/GABARAP is commonly used to monitor autophagosomes, a hallmark of autophagy, despite artifacts related to their overexpression. Here, we developed new sensors that detect endogenous LC3/GABARAP proteins at the autophagosome using an LC3-interacting region (LIR) and a short hydrophobic domain (HyD). Among HyD-LIR-GFP sensors harboring LIR motifs of 34 known LC3-binding proteins, HyD-LIR(TP)-GFP using the LIR motif from TP53INP2 allowed detection of all LC3/GABARAPs-positive autophagosomes...
March 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28320103/paeoniflorin-ameliorates-ages-induced-mesangial-cell-injury-through-inhibiting-rage-mtor-autophagy-pathway
#15
Juan Chen, Di Zhao, Maomao Zhu, Minghua Zhang, Xuefeng Hou, Wenbo Ding, Shuai Sun, Weiquan Bu, Liang Feng, Shiping Ma, Xiaobin Jia
Glomerular mesangial cell plays a vital role in diabetic nephropathy (DN). Recent research has demonstrated that autophagy involved in the development of DN. Paeoniflorin (PF), a monoterpene glucoside, has been proved to attenuate advanced glycation end products (AGEs)-induced mesangial cell injury. However, the regulatory mechanism of PF on autophagy in mesangial cell remains unclear. The aim of this study was to explore the effect of PF on autophagy in AGEs-induced mesangial cell dysfunction. In this study, the leakage of the lactic dehydrogenase (LDH) into the extracellular medium was measured by LDH kit...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28318354/hs1bp3-inhibits-autophagy-by-regulation-of-pld1
#16
Kristiane Søreng, Helene Knævelsrud, Petter Holland, Anne Simonsen
Macroautophagy/autophagy is a membrane trafficking and intracellular degradation process involving the formation of double-membrane autophagosomes and their ultimate fusion with lysosomes. Much is yet to be learned about the regulation of this process, especially at the level of the membranes and lipids involved. We have recently found that the PX domain protein HS1BP3 (HCLS1 binding protein 3) is a negative regulator of autophagosome formation. HS1BP3 depletion increases the formation of LC3-positive autophagosomes both in human cells and zebrafish...
February 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28318352/the-role-of-nlrp3-casp1-in-inflammasome-mediated-neuroinflammation-and-autophagy-dysfunction-in-manganese-induced-hippocampal-dependent-impairment-of-learning-and-memory-ability
#17
Diya Wang, Jianbin Zhang, Wenkai Jiang, Zipeng Cao, Fang Zhao, Tongjian Cai, Michael Aschner, Wenjing Luo
Central nervous system (CNS) inflammation and autophagy dysfunction are known to be involved in the pathology of neurodegenerative diseases. Manganese (Mn), a neurotoxic metal, has the potential to induce microglia-mediated neuroinflammation as well as autophagy dysfunction. NLRP3 (NLR family, pyrin domain containing 3)- CASP1 (caspase 1) inflammasome-mediated neuroinflammation in microglia has specific relevance to neurological diseases. However, the mechanism driving these phenomena remains poorly understood...
February 27, 2017: Autophagy
https://www.readbyqxmd.com/read/28306713/trypanocidal-effect-of-isotretinoin-through-the-inhibition-of-polyamine-and-amino-acid-transporters-in-trypanosoma-cruzi
#18
Chantal Reigada, Edward A Valera-Vera, Melisa Sayé, Andrea E Errasti, Carla C Avila, Mariana R Miranda, Claudio A Pereira
Polyamines are essential compounds to all living organisms and in the specific case of Trypanosoma cruzi, the causative agent of Chagas disease, they are exclusively obtained through transport processes since this parasite is auxotrophic for polyamines. Previous works reported that retinol acetate inhibits Leishmania growth and decreases its intracellular polyamine concentration. The present work describes a combined strategy of drug repositioning by virtual screening followed by in vitro assays to find drugs able to inhibit TcPAT12, the only polyamine transporter described in T...
March 17, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28306502/pacer-mediates-the-function-of-class-iii-pi3k-and-hops-complexes-in-autophagosome-maturation-by-engaging-stx17
#19
Xiawei Cheng, Xiuling Ma, Xianming Ding, Lin Li, Xiao Jiang, Zhirong Shen, She Chen, Wei Liu, Weihua Gong, Qiming Sun
Class III PI3-kinase (PI3KC3) is essential for autophagy initiation, but whether PI3KC3 participates in other steps of autophagy remains unknown. The HOPS complex mediates the fusion of intracellular vesicles to lysosome, but how HOPS specifically tethers autophagosome to lysosome remains elusive. Here, we report Pacer (protein associated with UVRAG as autophagy enhancer) as a regulator of autophagy. Pacer localizes to autophagic structures and positively regulates autophagosome maturation. Mechanistically, Pacer antagonizes Rubicon to stimulate Vps34 kinase activity...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28302910/new-insights-into-autophagosome-lysosome-fusion
#20
REVIEW
Shuhei Nakamura, Tamotsu Yoshimori
Macroautophagy (autophagy) is a highly conserved intracellular degradation system that is essential for homeostasis in eukaryotic cells. Due to the wide variety of the cytoplasmic targets of autophagy, its dysregulation is associated with many diseases in humans, such as neurodegenerative diseases, heart disease and cancer. During autophagy, cytoplasmic materials are sequestered by the autophagosome - a double-membraned structure - and transported to the lysosome for digestion. The specific stages of autophagy are induction, formation of the isolation membrane (phagophore), formation and maturation of the autophagosome and, finally, fusion with a late endosome or lysosome...
March 16, 2017: Journal of Cell Science
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