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https://www.readbyqxmd.com/read/29233874/autophagy-s-secret-life-secretion-instead-of-degradation
#1
REVIEW
Aurore Claude-Taupin, Jingyue Jia, Michal Mudd, Vojo Deretic
Autophagy is conventionally described as a degradative, catabolic pathway and a tributary to the lysosomal system where the cytoplasmic material sequestered by autophagosomes gets degraded. However, autophagosomes or autophagosome-related organelles do not always follow this route. It has recently come to light that autophagy can terminate in cytosolic protein secretion or release of sequestered material from the cells, rather than in their degradation. In this review, we address this relatively new but growing aspect of autophagy as a complex pathway, which is far more versatile than originally anticipated...
December 12, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/29233872/regulation-of-selective-autophagy-the-p62-sqstm1-paradigm
#2
REVIEW
Trond Lamark, Steingrim Svenning, Terje Johansen
In selective autophagy, cytoplasmic components are selected and tagged before being sequestered into an autophagosome by means of selective autophagy receptors such as p62/SQSTM1. In this review, we discuss how selective autophagy is regulated. An important level of regulation is the selection of proteins or organelles for degradation. Components selected for degradation are tagged, often with ubiquitin, to facilitate recognition by autophagy receptors. Another level of regulation is represented by the autophagy receptors themselves...
December 12, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/29233870/the-mammalian-ulk1-complex-and-autophagy-initiation
#3
REVIEW
Maria Zachari, Ian G Ganley
Autophagy is a vital lysosomal degradation pathway that serves as a quality control mechanism. It rids the cell of damaged, toxic or excess cellular components, which if left to persist could be detrimental to the cell. It also serves as a recycling pathway to maintain protein synthesis under starvation conditions. A key initial event in autophagy is formation of the autophagosome, a unique double-membrane organelle that engulfs the cytosolic cargo destined for degradation. This step is mediated by the serine/threonine protein kinase ULK1 (unc-51-like kinase 1), which functions in a complex with at least three protein partners: FIP200 (focal adhesion kinase family interacting protein of 200 kDa), ATG (autophagy-related protein) 13 (ATG13), and ATG101...
December 12, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/29233105/salidroside-attenuates-hypoxia-induced-pulmonary-arterial-smooth-muscle-cell-proliferation-and-apoptosis-resistance-by-upregulating-autophagy-through-the-ampk-mtor-ulk1-pathway
#4
Di Gui, Zhimin Cui, Lin Zhang, Chang Yu, Dan Yao, Min Xu, Mayun Chen, Peiliang Wu, Guoping Li, Liangxing Wang, Xiaoying Huang
BACKGROUND: Recent studies have shown that both adenosine monophosphate activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR) are energy sensors and are related to autophagy. Our recent reports have shown that salidroside can exert protective effects against hypoxia-induced pulmonary arterial smooth muscle cell (PASMC) proliferation and apoptosis resistance through the AMPK pathway. This study aims to explore the relationship among AMPK, mTOR and ULK1 in PASMCs under hypoxic conditions and to investigate whether the protective effects of salidroside are related to the autophagic cell death pathway...
December 12, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29232556/mst4-phosphorylation-of-atg4b-regulates-autophagic-activity-tumorigenicity-and-radioresistance-in-glioblastoma
#5
Tianzhi Huang, Chung Kwon Kim, Angel A Alvarez, Rajendra P Pangeni, Xuechao Wan, Xiao Song, Taiping Shi, Yongyong Yang, Namratha Sastry, Craig M Horbinski, Songjian Lu, Roger Stupp, John A Kessler, Ryo Nishikawa, Ichiro Nakano, Erik P Sulman, Xinghua Lu, Charles David James, Xiao-Ming Yin, Bo Hu, Shi-Yuan Cheng
ATG4B stimulates autophagy by promoting autophagosome formation through reversible modification of ATG8. We identify ATG4B as a substrate of mammalian sterile20-like kinase (STK) 26/MST4. MST4 phosphorylates ATG4B at serine residue 383, which stimulates ATG4B activity and increases autophagic flux. Inhibition of MST4 or ATG4B activities using genetic approaches or an inhibitor of ATG4B suppresses autophagy and the tumorigenicity of glioblastoma (GBM) cells. Furthermore, radiation induces MST4 expression, ATG4B phosphorylation, and autophagy...
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29230855/a-role-for-autophagy-in-long-term-spatial-memory-formation-in-male-rodents
#6
Michael J Hylin, Jing Zhao, Karthikeyan Tangavelou, Natalia S Rozas, Kimberly N Hood, Jacalyn S MacGowan, Anthony N Moore, Pramod K Dash
A hallmark of long-term memory formation is the requirement for protein synthesis. Administration of protein synthesis inhibitors impairs long-term memory formation without influencing short-term memory. Rapamycin is a specific inhibitor of target of rapamycin complex 1 (TORC1) that has been shown to block protein synthesis and impair long-term memory. In addition to regulating protein synthesis, TORC1 also phosphorylates Unc-51-like autophagy activating kinase-1 (Ulk-1) to suppress autophagy. As autophagy can be activated by rapamycin (and rapamycin inhibits long-term memory), our aim was to test the hypothesis that autophagy inhibitors would enhance long-term memory...
December 12, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29230547/novel-fluorochromes-label-tonoplast-in-living-plant-cells-and-reveal-changes-in-vacuolar-organization-after-treatment-with-protein-phosphatase-inhibitors
#7
Miklós Nagy, Sándor Kéki, Dávid Rácz, Jaideep Mathur, György Vereb, Tamás Garda, Márta M-Hamvas, François Chaumont, Károly Bóka, Béla Böddi, Csongor Freytag, Gábor Vasas, Csaba Máthé
The recently synthesized isocyanonaphtalene derivatives ACAIN and CACAIN are fluorochromes excitable at wavelengths of around 366 nm and bind cysteine-rich proteins with hydrophobic motifs. We show that these compounds preferentially label tonoplasts in living Arabidopsis and tobacco (Nicotiana tabacum SR1) cells. ACAIN-labeled membranes co-localized with the GFP signal in plants expressing GFP-δ-TIP (TIP2;1) (a tonoplast aquaporin) fusion protein. ACAIN preserved the dynamics of vacuolar structures. tip2;1 and triple tip1;1-tip1;2-tip2;1 knockout mutants showed weaker ACAIN signal in tonoplasts...
December 12, 2017: Protoplasma
https://www.readbyqxmd.com/read/29230347/induction-of-reactive-intermediates-and-autophagy-related-proteins-upon-infection-of-macrophages-with-rhodococcus-equi
#8
Prashanth Chandramani-Shivalingappa, Mahesh Bhandari, Sarah A Wiechert, Jessica Gilbertie, Douglas E Jones, Brett A Sponseller
Rhodococcus equi (R. equi) is an intracellular macrophage-tropic pathogen with potential for causing fatal pyogranulomatous pneumonia in foals between 1 and 6 months of age. In this study, we sought to determine whether infection of macrophages with R. equi could lead to the induction of autophagy. Murine bone marrow derived macrophages (BMDM) were infected with R. equi for various time intervals and analyzed for upregulation of autophagy proteins and accumulation of autophagosomes relative to uninfected controls...
2017: Scientifica
https://www.readbyqxmd.com/read/29229996/rab37-interacts-directly-with-atg5-and-promotes-autophagosome-formation-via-regulating-atg5-12-16-complex-assembly
#9
Yue Sheng, Ying Song, Zhigang Li, Yabo Wang, Heming Lin, Hanhua Cheng, Rongjia Zhou
Intracellular membrane trafficking is essential for eukaryotic cell existence. Here, we show that RAB37 activation through GTP binding recruits ATG5-12 to isolation membrane and promotes autophagosome formation through the ATG5-ATG12-ATG16L1 complex. RAB37 is localized on the isolation membrane. It can bind directly with ATG5 and promotes formation of the ATG5-12-16 complex. Mutation analysis reveals that GTP-bound RAB37 exhibits an enhanced interaction with ATG5-12 and GDP-stabilised mutation impairs the interaction...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29229534/a-novel-compound-dt-010-protects-against-doxorubicin-induced-cardiotoxicity-in-zebrafish-and-h9c2-cells-by-inhibiting-reactive-oxygen-species-mediated-apoptotic-and-autophagic-pathways
#10
Fan Tang, Xinhua Zhou, Liang Wang, Luchen Shan, Chuwen Li, Hefeng Zhou, Simon Ming-Yuen Lee, Maggie Pui-Man Hoi
Doxorubicin (Dox) is an effective anti-cancer agent but limited by its cardiotoxicity, thus the search for pharmacological agents for enhancing anti-cancer activities and protecting against cardiotoxicity has been a subject of great interest. We have previously reported the synergistic anti-cancer effects of a novel compound DT-010. In the present study, we further investigated the cardioprotective effects of DT-010 in zebrafish embryos in vivo and the molecular underlying mechanisms in H9c2 cardiomyocytes in vitro...
December 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29228719/levels-of-leydig-cell-autophagy-regulate-the-fertility-of-male-naked-mole-rats
#11
Wenjing Yang, Li Li, Xiaofeng Huang, Guanghan Kan, Lifang Lin, Jishuai Cheng, Chen Xu, Wei Sun, Wei Cong, Shanmin Zhao, Shufang Cui
Fertility is abolished in nonbreeding males in colonies of natal naked mole-rats (NMRs). Although spermatogenesis occurs in both breeding and nonbreeding male NMRs, the mechanisms underlying the differences in fertility between breeders and nonbreeders remain unexplored. In this study, a significant decrease in autophagy was observed in Leydig cells of the testis from nonbreeding male NMRs. This alteration was visualised as a significant decrease in the levels of autophagy-related gene 7 (Atg7), Atg5, microtubule-associated protein 1A/B light chain 3 (LC3-II/I) and the number of autophagosomes and an increase in P62 levels using Western blotting analyses...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227549/in-vitro-dissection-of-autophagy
#12
Min Zhang, Dawei Liu, Liang Ge
Autophagy is an essential cellular process for bulk degradation of cytoplasmic components through the lysosome. Underlying this process is an intricate interaction between protein factors and the cell endomembrane system, leading to a gradual maturation of the autophagic membrane. This structure sequesters a portion of the cytoplasm by the formation of a double-membrane compartment called the autophagosome. The autophagosome then delivers the cargo to the lysosome to complete degradation. The molecular mechanism accounting for the generation of the autophagic membrane is a longstanding question...
December 11, 2017: Current Protocols in Cell Biology
https://www.readbyqxmd.com/read/29218765/deregulation-of-autophagy-in-postmortem-brains-of-machado-joseph-disease-patients
#13
Annie Sittler, Marie-Paule Muriel, Martina Marinello, Alexis Brice, Wilfred den Dunnen, Sandro Alves
Autophagy, the major pathway for protein turnover, is critical to maintain cellular homeostasis and has been implicated in neurodegenerative diseases. The aim of this research was to analyze the expression of autophagy markers in postmortem brains from Machado-Joseph disease (MJD) patients. The expression of autophagy markers in the cerebellum and the oculomotor nucleus from MJD patients and age-matched controls with no signs of neuropathology was inspected postmortem by immunohistochemistry (IHC) and Western blot...
December 8, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/29218074/autophagy-in-endometriosis
#14
REVIEW
Hui-Li Yang, Jie Mei, Kai-Kai Chang, Wen-Jie Zhou, Li-Qing Huang, Ming-Qing Li
Endometriosis (EMS) is a common gynecologic disease that causes chronic pelvic pain, dysmenorrhea, and infertility in women. The doctrine of menstruation back flow planting and defects in the immune system are well known and widely accepted. In recent years, increasing studies have been focused on the role of autophagy in EMS, and have shown that autophagy plays a vital role in EMS. Autophagy, which is known as the non-apoptotic form of programmed cell death induced by a large number of intracellular/extracellular stimuli, is the major cellular pathway for the degradation of long-lived proteins and cytoplasmic organelles in eukaryotic cells...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29215417/muramyl-dipeptide-enhances-thermal-injury-induced-autophagy-and-inflammatory-cytokine-response-of-lungs-via-activation-of-nod2-rick-signaling-pathway-in-rats
#15
Xiao-Jing Wu, Hui Liang, Ying Zhang, Xu-Ming Yang, Hong-Yu Wang, Hui Li, Xin-Yi Li, Kai Chen, Yan-Lin Wang, Jian-Guo Li, Zong-Ze Zhang, Xue-Min Song
OBJECTIVE: Nucleotide-binding oligomerization domain 2 (NOD2) is the innate receptor of muramyl dipeptide (MDP). Our previous study revealed that MDP could enhance thermal injury-induced inflammatory cytokine production and organ function injury in rats. The present study was to determine the effect of MDP on autophagy and NOD2/receptor-interacting serine/threonine protein kinases (RICK) signaling pathway of lung injury after thermal injury. METHODS: Forty male Sprague-Dawlay rats were randomly divided into four groups: normal control (NC) group, MDP group, Scald group and MDP + Scald group...
December 6, 2017: Shock
https://www.readbyqxmd.com/read/29212935/tetraspanin-cd63-bridges-autophagic-and-endosomal-processes-to-regulate-exosomal-secretion-and-intracellular-signaling-of-epstein-barr-virus-lmp1
#16
Stephanie N Hurwitz, Mujeeb R Cheerathodi, Dingani Nkosi, Sara B York, David G Meckes
The tetraspanin protein CD63 has been recently described as a key factor in extracellular vesicle (EV) production and endosomal cargo sorting. In the context of Epstein-Barr virus (EBV) infection, CD63 is required for the efficient packaging of the major viral oncoprotein latent membrane protein 1 (LMP1) into exosomes and other EV populations, and acts as a negative regulator of LMP1 intracellular signaling. Accumulating evidence has also pointed to intersections of the endosomal and autophagy pathways in maintaining cellular secretory processes, and as sites for viral assembly and replication...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29212187/autophagy-protein-lc3-regulates-the-fibrosis-of-hypertrophic-scar-by-controlling-bcl-xl-in-dermal-fibroblasts
#17
Jihong Shi, Shan Shi, Bin Wu, Jian Zhang, Yan Li, Xue Wu, Julei Zhang, Kejia Wang, Bin Zhao, Weixia Cai, Xiaozhi Bai, Dahai Hu, Hao Guan
Hypertrophic scar (HS) is a serious skin fibrotic disease characterized by excessive hypercellularity and extracellular matrix (ECM) component deposition. Autophagy is a tightly regulated physiological process essential for cellular maintenance, differentiation, development and homeostasis. However, during the formation of HS, whether and how autophagy is regulated in dermal fibroblasts are still far from elucidated. Here we detected the autophagic capacity in HS and normal skin (NS) counterparts, explored and verified the key regulatory molecules of autophagy in HS-derived fibroblasts (HSFs), and validated the data using rabbit ear scar model...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29210078/mdatg18a-overexpression-improves-tolerance-to-nitrogen-deficiency-and-regulates-anthocyanin-accumulation-through-increased-autophagy-in-transgenic-apple
#18
Xun Sun, Xin Jia, Liuqing Huo, Runmin Che, Xiaoqing Gong, Ping Wang, Fengwang Ma
Nitrogen (N) availability is an essential factor for plant growth. Recycling and remobilization of N have strong impacts on crop yield and quality under N deficiency. Autophagy is a critical nutrient-recycling process that facilitates remobilization under starvation. We previously showed that an important AuTophaGy (ATG) protein from apple, MdATG18a, has a positive role in drought tolerance. In this study, we explored its biological role in response to low-N. Overexpression of MdATG18a in both Arabidopsis and apple improved tolerance to N-depletion and caused a greater accumulation of anthocyanin...
December 5, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/29209653/unveiling-the-role-of-vps34-kinase-domain-dynamics-in-regulation-of-the-autophagic-pi3k-complex
#19
Goran Stjepanovic, Sulochanadevi Baskaran, Mary G Lin, James H Hurley
The class III PI 3-kinase, VPS34 forms distinct complexes essential for cargo sorting and membrane trafficking in endocytosis as well as for autophagosome nucleation and maturation. We used integrative structural biology approach to provide insights into the conformational dynamics of the complex and mechanisms that regulate VPS34 activity at the membrane.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29209172/the-role-of-netrin-1-in-improving-functional-recovery-through-autophagy-stimulation-following-spinal-cord-injury-in-rats
#20
Liangjie Bai, Xifan Mei, Yanfeng Wang, Yajiang Yuan, Yunlong Bi, Gang Li, Hongyu Wang, Peng Yan, Gang Lv
Our previous findings indicated that treatment with Netrin-1 could improve functional recovery through the stimulation of autophagy, by activating the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway in rats following spinal cord injury (SCI). However, the underlying mechanisms were not elucidated. The purpose of this study was to investigate the underlying mechanisms by which Netrin-1 promotes autophagy and improves functional recovery after SCI. Following controlled SCI in Sprague-Dawley rats, we observed that the autophagic flux in neurons was impaired, as reflected by the accumulation of light chain 3-II (LC3-II)-positive and LC3-positive autophagosomes (APs), accompanied by the accumulation of the autophagic substrate, Sequestosome 1 (SQSTM1; also known as p62)...
2017: Frontiers in Cellular Neuroscience
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