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Selective autophagy

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https://www.readbyqxmd.com/read/29331651/activation-of-p62-keap1-nrf2-antioxidant-pathway-in-the-early-stage-of-acetaminophen-induced-acute-liver-injury-in-mice
#1
Zhenyu Shen, Yu Wang, Zhenhui Su, Ruirui Kou, Keqin Xie, Fuyong Song
Acetaminophen (APAP) overdose can cause severe liver failure even death. Nearly half of drug-induced liver injury is attributed to APAP in the US and many European countries. Oxidative stress has been validated as a critical event involved in APAP-induced liver failure. p62/SQSTM1, a selective autophagy adaptor protein, is reported to regulate Nrf2-ARE antioxidant pathway in response to oxidative stress. However, the exact role of p62-keap1-Nrf2 antioxidant pathway in APAP-induced hepatotoxicity remains unknown...
January 10, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29330382/sesn2-facilitates-mitophagy-by-helping-parkin-translocation-through-ulk1-mediated-beclin1-phosphorylation
#2
Ashish Kumar, Chandrima Shaha
Mitophagy, the selective degradation of mitochondria by autophagy, is crucial for the maintenance of healthy mitochondrial pool in cells. The critical event in mitophagy is the translocation of cytosolic Parkin, a ubiquitin ligase, to the surface of defective mitochondria. This study elucidates a novel role of SESN2/Sestrin2, a stress inducible protein, in mitochondrial translocation of PARK2/Parkin during mitophagy. The data demonstrates that SESN2 downregulation inhibits BECN1/Beclin1 and Parkin interaction, thereby preventing optimum mitochondrial accumulation of Parkin...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329306/lifespan-extension-without-fertility-reduction-following-dietary-addition-of-the-autophagy-activator-torin1-in-drosophila-melanogaster
#3
Janet S Mason, Tom Wileman, Tracey Chapman
Autophagy is a highly conserved mechanism for cellular repair that becomes progressively down-regulated during normal ageing. Hence, manipulations that activate autophagy could increase lifespan. Previous reports show that manipulations to the autophagy pathway can result in longevity extension in yeast, flies, worms and mammals. Under standard nutrition, autophagy is inhibited by the nutrient sensing kinase Target of Rapamycin (TOR). Therefore, manipulations of TOR that increase autophagy may offer a mechanism for extending lifespan...
2018: PloS One
https://www.readbyqxmd.com/read/29328502/hepatocellular-carcinoma-related-cyclin-d1-is-selectively-regulated-by-autophagy-degradation-system
#4
Shan-Ying Wu, Sheng-Hui Lan, Shang-Rung Wu, Yen-Chi Chiu, Xi-Zhang Lin, Ih-Jen Su, Ting-Fen Tsai, Chia-Jui Yen, Tsung-Hsueh Lu, Fu-Wen Liang, Chung-Yi Li, Huey-Jen Su, Chun-Li Su, Hsiao-Sheng Liu
Dysfunction of degradation machineries causes cancers, including hepatocellular carcinoma (HCC). Overexpression of cyclin D1 in HCC has been reported. We previously reported that autophagy preferentially recruits and degrades the oncogenic miR-224 to prevent HCC. Therefore, in the present study we attempted to clarify whether cyclin D1 is another oncogenic factor selectively regulated by autophagy in HCC tumorigenesis. Initially, we found an inverse correlation between low autophagic activity and high cyclin D1 expression in the tumors of 147 HCC patients and three murine models, and these results taken together revealed a correlation with poor overall survival of HCC patients, indicating the importance of these two events in HCC development...
January 12, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29328421/antitumor-activity-of-curcumin-by-modulation-of-apoptosis-and-autophagy-in-human-lung-cancer-a549-cells-through-inhibiting-pi3k-akt-mtor-pathway
#5
Furong Liu, Song Gao, Yuxuan Yang, Xiaodan Zhao, Yameng Fan, Wenxia Ma, Danrong Yang, Aimin Yang, Yan Yu
Curcumin is known to exhibit anticancer effects on various cancers with selective cytotoxicity in tumor cells. In the present study, the effects of curcumin‑induced multiple PCDs on human non‑small cell lung cancer (NSCLC) cells and the potential molecular mechanisms of apoptosis and autophagy triggered by curcumin via the PI3K/Akt/mTOR signaling pathway were explored, further confirmed by co‑culture of curcumin with mTOR blocker rapamycin and PI3K/Akt inhibitor LY294002. The anti‑proliferation effect of different stimulus was measured by MTT assay...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29328391/effects-of-thymosin-%C3%AE-4-on-oxygen%C3%A2-glucose-deprivation-and-reoxygenation%C3%A2-induced-injury
#6
Hua Ji, Linhao Xu, Zheng Wang, Xinli Fan, Lihui Wu
Cerebral ischemia causes severe brain injury and results in selective neuronal death through programmed cell death mechanisms, including apoptosis and autophagy. Minimizing neuronal injury has been considered a hot topic among clinicians. The present study elucidated the effect of thymosin β4 (Tβ4) on neuronal death induced by cerebral ischemia/reperfusion in PC12 cells that were subjected to oxygen‑glucose deprivation and reoxygenation (OGD/R). The survival, apoptotic and autophagy rates of PC12 cells were investigated...
January 9, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29326381/b1a-b-cells-require-autophagy-for-metabolic-homeostasis-and-self-renewal
#7
Alexander J Clarke, Thomas Riffelmacher, Daniel Braas, Richard J Cornall, Anna Katharina Simon
Specific metabolic programs are activated by immune cells to fulfill their functional roles, which include adaptations to their microenvironment. B1 B cells are tissue-resident, innate-like B cells. They have many distinct properties, such as the capacity to self-renew and the ability to rapidly respond to a limited repertoire of epitopes. The metabolic pathways that support these functions are unknown. We show that B1 B cells are bioenergetically more active than B2 B cells, with higher rates of glycolysis and oxidative phosphorylation, and depend on glycolysis...
January 11, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29325609/the-cag-polyglutamine-repeat-diseases-a-clinical-molecular-genetic-and-pathophysiologic-nosology
#8
Colleen A Stoyas, Albert R La Spada
Throughout the genome, unstable tandem nucleotide repeats can expand to cause a variety of neurologic disorders. Expansion of a CAG triplet repeat within a coding exon gives rise to an elongated polyglutamine (polyQ) tract in the resultant protein product, and accounts for a unique category of neurodegenerative disorders, known as the CAG-polyglutamine repeat diseases. The nine members of the CAG-polyglutamine disease family include spinal and bulbar muscular atrophy (SBMA), Huntington disease, dentatorubral pallidoluysian atrophy, and six spinocerebellar ataxias (SCA 1, 2, 3, 6, 7, and 17)...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29322304/causative-genes-in-amyotrophic-lateral-sclerosis-and-protein-degradation-pathways-a-link-to-neurodegeneration
#9
REVIEW
C Maurel, A Dangoumau, S Marouillat, C Brulard, A Chami, R Hergesheimer, P Corcia, H Blasco, C R Andres, P Vourc'h
Amyotrophic lateral sclerosis (ALS) is a disease caused by the degeneration of motor neurons (MNs) leading to progressive muscle weakness and atrophy. Several molecular pathways have been implicated, such as glutamate-mediated excitotoxicity, defects in cytoskeletal dynamics and axonal transport, disruption of RNA metabolism, and impairments in proteostasis. ALS is associated with protein accumulation in the cytoplasm of cells undergoing neurodegeneration, which is a hallmark of the disease. In this review, we focus on mechanisms of proteostasis, particularly protein degradation, and discuss how they are related to the genetics of ALS...
January 10, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29321961/biophysical-characterization-of-atg11-a-scaffold-protein-essential-for-selective-autophagy-in-yeast
#10
Hironori Suzuki, Nobuo N Noda
Autophagy is an intracellular degradation system in which the formation of an autophagosome is a key event. In budding yeast, autophagosomes are generated from the preautophagosomal structure (PAS), in which Atg11 and Atg17 function as scaffolds essential for selective and nonselective types of autophagy, respectively. Structural studies have been extensively performed on Atg17, but not on Atg11, preventing us from understanding the selective type of the PAS. Here, we purified and characterized Atg11. Biophysical analyses, including analytical ultracentrifugation and CD, showed that Atg11 behaves as an elongated homodimer abundant in α-helices in solution...
January 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29321306/digitoxin-suppresses-human-cytomegalovirus-replication-via-na-k-atpase-%C3%AE-1-subunit-dependent-ampk-and-autophagy-activation
#11
Rupkatha Mukhopadhyay, Rajkumar Venkatadri, Jenny Katsnelson, Ravit Arav-Boger
Host-directed therapeutics for human cytomegalovirus (HCMV) requires elucidation of cellular mechanisms that inhibit HCMV. We report on a novel pathway used by cardiac glycosides to inhibit HCMV replication: induction of AMPK activity and autophagy flux through the Na+, K+/ATPase α1 subunit. Our data illustrate an intricate balance between autophagy regulators AMPK, mTOR and ULK1 during infection and treatment with the cardiac glycoside, digitoxin. Both infection and digitoxin induced AMPK phosphorylation, but ULK1 was differentially phosphorylated at unique sites leading to opposing effects on autophagy...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29320480/pharmacological-activation-of-rev-erbs-is-lethal-in-cancer-and-oncogene-induced-senescence
#12
Gabriele Sulli, Amy Rommel, Xiaojie Wang, Matthew J Kolar, Francesca Puca, Alan Saghatelian, Maksim V Plikus, Inder M Verma, Satchidananda Panda
The circadian clock imposes daily rhythms in cell proliferation, metabolism, inflammation and DNA damage response. Perturbations of these processes are hallmarks of cancer and chronic circadian rhythm disruption predisposes individuals to tumour development. This raises the hypothesis that pharmacological modulation of the circadian machinery may be an effective therapeutic strategy for combating cancer. REV-ERBs, the nuclear hormone receptors REV-ERBα (also known as NR1D1) and REV-ERBβ (also known as NR1D2), are essential components of the circadian clock...
January 10, 2018: Nature
https://www.readbyqxmd.com/read/29317452/autophagy-sustains-pancreatic-cancer-growth-through-both-cell-autonomous-and-non-autonomous-mechanisms
#13
Annan Yang, Grit Herter-Sprie, Haikuo Zhang, Elaine Y Lin, Douglas Biancur, Xiaoxu Wang, Jiehui Deng, Josephine Hai, Shenghong Yang, Kwok-Kin Wong, Alec C Kimmelman
Autophagy has been shown to be elevated in pancreatic adenocarcinoma (PDAC) and its role in promoting established tumor growth has made it a promising therapeutic target. However, due to limitations of prior mouse models as well as the lack of potent and selective autophagy inhibitors, the ability to fully assess the mechanistic basis of how autophagy supports pancreatic cancer has been limited. To test the feasibility of treating PDAC using autophagy inhibition and further our understanding of the mechanisms of pro-tumor effects of autophagy, we developed a novel mouse model that allowed the acute and reversible inhibition of autophagy...
January 9, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29313416/dicot-specific-atg8-interacting-ati3-proteins-interact-with-conserved-ubac2-proteins-and-play-critical-roles-in-plant-stress-responses
#14
Jie Zhou, Zhe Wang, Xiaoting Wang, Xifeng Li, Zhenchao Zhang, Baofang Fan, Cheng Zhu, Zhixiang Chen
Selective macroautophagy/autophagy targets specific cargo by autophagy receptors through interaction with ATG8 (autophagy-related protein 8)/MAP1LC3 (microtubule associated protein 1 light chain 3) for degradation in the vacuole. Here, we report the identification and characterization of 3 related ATG8-interacting proteins (AT1G17780/ATI3A, AT2G16575/ATI3B and AT1G73130/ATI3C) from Arabidopsis. ATI3 proteins contain a WxxL LC3-interacting region (LIR) motif at the C terminus required for interaction with ATG8...
January 9, 2018: Autophagy
https://www.readbyqxmd.com/read/29309625/autophagy-in-turnover-of-lipid-stores-trans-kingdom-comparison
#15
Pernilla H Elander, Elena A Minina, Peter V Bozhkov
Lipids and their cellular utilization are essential for life. Not only are lipids energy storage molecules, but their diverse structural and physical properties underlie various aspects of eukaryotic biology, such as membrane structure, signalling, and trafficking. In the ever-changing environment of cells, lipids, like other cellular components, are regularly recycled to uphold the housekeeping processes required for cell survival and organism longevity. The ways in which lipids are recycled, however, vary between different phyla...
December 23, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29308895/highly-selective-potent-and-oral-mtor-inhibitor-for-treatment-of-cancer-as-autophagy-inducer
#16
Qingxiang Guo, Chenhua Yu, Chao Zhang, Yongtao Li, Tianqi Wang, Zhi Huang, Xin Wang, Wei Zhou, Yao Li, Zhongxiang Qin, Cheng Wang, Ruifang Gao, Yongwei Nie, Yakun Ma, Yi Shi, Jian-Yu Zheng, Shengyong Yang, Yan Fan, Rong Xiang
Based on novel pyrazino[2,3-c]quinolin-2(1H)-one scaffold, we designed and identified a highly selective, potent and oral mTOR inhibitor, 9m. Compound 9m showed low nanomolar activity against mTOR (IC50 =7 nM) and greater selectivity over the related PIKK family kinases, which demonstrated only modest activity against 3 out of the 409 protein kinases. In vitro assays, compound 9m exhibited high potency against human breast and cervical cancer cells and induced tumor cell cycle arrest and autophagy. 9m inhibited cellular phosphorylation of mTOR1 (pS6, and p4E-BP1) and mTOR2 (pAKT (S473)) substrates...
January 8, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29305265/the-nem1-spo7-protein-phosphatase-complex-is-required-for-efficient-mitophagy-in-yeast
#17
Xueyan Xu, Koji Okamoto
Mitochondria-targeted selective autophagy, termed mitophagy, is an evolutionarily conserved process that contributes to mitochondrial quantity and quality control. Mitophagy requires elaborate membrane biogenesis of autophagosomes surrounding mitochondria, although how this process is regulated remains obscure. We show here that mitophagy is strongly suppressed in yeast cells lacking Nem1 or Spo7, two proteins forming a heterodimeric protein phosphatase complex known to be important for proper shaping of the nucleus and endoplasmic reticulum (ER)...
January 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29296191/3-methyladenine-ameliorates-liver-fibrosis-through-autophagy-regulated-by-the-nf-%C3%AE%C2%BAb-signaling-pathways-on-hepatic-stellate-cell
#18
Bingying Wang, Huan Yang, Yinyin Fan, Yong Yang, Wei Cao, Yanwei Jia, Ying Cao, Kangyun Sun, Zhi Pang, Hong Du
3-Methyladenine (3-MA) is a selective type III phosphatidylinositol 3-kinase (PI3K) inhibitor and also blocks autophagosome formation. However, the effect of 3-MA in liver fibrosis has yet to be determined. Recent studies have demonstrated that autophagy is closely related to activation of hepatic stellate cells (HSC), a process critical in the pathogenesis of liver fibrosis. And the transcription factor nuclear factor-kappaB (NF-κB) is proved to play an important role in autophagy-induced signaling pathways...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29291012/alisertib-promotes-apoptosis-and-autophagy-in-melanoma-through-p38-mapk-mediated-aurora-a-signaling
#19
Yuan-Yuan Shang, Ming Yao, Zhi-Wei Zhou, Jian-Cui, Li-Xia, Rong-Ying Hu, Ying-Yao Yu, Qiong-Gao, Biao-Yang, Yu-Xi Liu, Jie Dang, Shu-Feng Zhou, Nan-Yu
We investigated the efficacy of Alisertib (ALS), a selective Aurora kinase A (AURKA) inhibitor, in melanoma. We found that ALS exerts anti-proliferative, pro-apoptotic, and pro-autophagic effects on A375 and skmel-5 melanoma cells by inhibiting p38 MAPK signaling. SB202190, a p38 MAPK-selective inhibitor, enhanced ALS-induced apoptosis and autophagy in both cell lines. ALS induced cell cycle arrest in melanoma cells through activation of the p53/p21/cyclin B1 pathway. Knockdown of p38 MAPK enhanced ALS-induced apoptosis and reduced ALS-induced autophagy...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290589/ccpg1-is-a-non-canonical-autophagy-cargo-receptor-essential-for-er-phagy-and-pancreatic-er-proteostasis
#20
Matthew D Smith, Margaret E Harley, Alain J Kemp, Jimi Wills, Martin Lee, Mark Arends, Alex von Kriegsheim, Christian Behrends, Simon Wilkinson
Mechanisms of selective autophagy of the ER, known as ER-phagy, require molecular delineation, particularly in vivo. It is unclear how these events control ER proteostasis and cellular health. Here, we identify cell-cycle progression gene 1 (CCPG1), an ER-resident protein with no known physiological role, as a non-canonical cargo receptor that directly binds to core autophagy proteins via an LIR motif to mammalian ATG8 proteins and, independently and via a discrete motif, to FIP200. These interactions facilitate ER-phagy...
December 27, 2017: Developmental Cell
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