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Source: Autophagy

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Total 127 results found since Jan 2013.

Identification of modulators of autophagic flux in an image-based high content siRNA screen.
Abstract Autophagy is the primary process for recycling cellular constituents through lysosomal degradation. In addition to nonselective autophagic engulfment of cytoplasm, autophagosomes can recognize specific cargo by interacting with ubiquitin-binding autophagy receptors such as SQSTM1/p62 (sequestosome 1). This selective form of autophagy is important for degrading aggregation-prone proteins prominent in many neurodegenerative diseases. We carried out a high content image-based siRNA screen (4 to 8 siRNA per gene) for modulators of autophagic flux by monitoring fluorescence of GFP-SQSTM1 as well as colocalizat...
Source: Autophagy - April 1, 2016 Category: Cytology Authors: Hale CM, Cheng Q, Ortuno D, Huang M, Nojima D, Kassner PD, Wang S, Ollmann MM, Carlisle HJ Tags: Autophagy Source Type: research

Endothelial autophagy deficiency induces IL6 - dependent endothelial mesenchymal transition and organ fibrosis.
Abstract Macroautophagy/autophagy plays a vital role in the homeostasis of diverse cell types. Vascular endothelial cells contribute to vascular health and play a unique role in vascular biology. Here, we demonstrated that autophagy defects in endothelial cells induced IL6 (interleukin 6)-dependent endothelial-to-mesenchymal transition (EndMT) and organ fibrosis with metabolic defects in mice. Inhibition of autophagy, either by a specific inhibitor or small interfering RNA (siRNA) for ATG5 (autophagy related 5), in human microvascular endothelial cells (HMVECs) induced EndMT. The IL6 level was significantly higher...
Source: Autophagy - January 21, 2020 Category: Cytology Authors: Takagaki Y, Lee SM, Dongqing Z, Kitada M, Kansaki K, Koya D Tags: Autophagy Source Type: research

BIX-01294 induces autophagy-associated cell death via EHMT2/G9a dysfunction and intracellular reactive oxygen species production.
Abstract We screened a chemical library in MCF-7 cells stably expressing green fluorescent protein (GFP)-conjugated microtubule-associated protein 1 light chain 3 (LC3) (GFP-LC3-MCF-7) using cell-based assay, and identified BIX-01294 (BIX), a selective inhibitor of euchromatic histone-lysine N-methyltransferase 2 (EHMT2), as a strong autophagy inducer. BIX enhanced formation of GFP-LC3 puncta, LC3-II, and free GFP, signifying autophagic activation. Inhibition of these phenomena with chloroquine and increasement in punctate dKeima ratio (550/438) signal indicated that BIX activated autophagic flux. BIX-induced cell...
Source: Autophagy - December 1, 2013 Category: Cytology Authors: Kim Y, Kim YS, Kim DE, Lee JS, Song JH, Kim HG, Cho DH, Jeong SY, Jin DH, Jang SJ, Seol HS, Suh YA, Lee SJ, Kim CS, Koh JY, Hwang JJ Tags: Autophagy Source Type: research

TXNDC17 promotes paclitaxel resistance via inducing autophagy in ovarian cancer.
Abstract Paclitaxel is recommended as a first-line chemotherapeutic agent against ovarian cancer, but drug resistance becomes a major limitation of its success clinically. The key molecule or mechanism associated with paclitaxel resistance in ovarian cancer still remains unclear. Here, we showed that TXNDC17 screened from 356 differentially expressed proteins by LC-MS/MS label-free quantitative proteomics was more highly expressed in paclitaxel-resistant ovarian cancer cells and tissues, and the high expression of TXNDC17 was associated with poorer prognostic factors and exhibited shortened survival in 157 ovaria...
Source: Autophagy - January 21, 2015 Category: Cytology Authors: Zhang SF, Wang XY, Fu ZQ, Peng QH, Zhang JY, Ye F, Fu YF, Zhou CY, Lu WG, Cheng XD, Xie X Tags: Autophagy Source Type: research

The human CD5L/AIM-CD36 axis: A novel autophagy inducer in macrophages that modulates inflammatory responses.
Abstract CD5L (CD5 molecule-like) is a secreted glycoprotein that participates in host response to bacterial infection. CD5L influences the monocyte inflammatory response to the bacterial surface molecules lipopolysaccharide (LPS) and lipoteichoic acid (LTA) by inhibiting TNF secretion. Here we studied the intracellular events that lead to macrophage TNF inhibition by human CD5L. To accomplish this goal, we performed functional analyses with human monocytic THP1 macrophages, as well as with peripheral blood monocytes. Inhibition of phosphatidylinositol 3-kinase (PtdIns3K) reversed the inhibitory effect of CD5L on ...
Source: Autophagy - February 25, 2015 Category: Cytology Authors: Sanjurjo L, Amézaga N, Aran G, Naranjo-Gómez M, Arias L, Armengol C, Borràs FE, Sarrias MR Tags: Autophagy Source Type: research

Loss of autophagy enhances MIF/macrophage migration inhibitory factor release by macrophages.
Abstract MIF (macrophage migration inhibitory factor [glycosylation-inhibiting factor]) is a pro-inflammatory cytokine expressed in multiple cells types, including macrophages. MIF plays a pathogenic role in a number of inflammatory diseases and has been linked to tumor progression in some cancers. Previous work has demonstrated that loss of autophagy in macrophages enhances secretion of IL1 family cytokines. Here, we demonstrate that loss of autophagy, by pharmacological inhibition or siRNA silencing of Atg5, enhances MIF secretion by monocytes and macrophages. We further demonstrate that this is dependent on mit...
Source: Autophagy - May 9, 2016 Category: Cytology Authors: Lee JP, Foote A, Fan H, de Castro CP, Lang T, Jones SA, Gavrilescu N, Mills KH, Leech M, Morand EF, Harris J Tags: Autophagy Source Type: research

Deletion of PRKAA triggers mitochondrial fission by inhibiting the autophagy-dependent degradation of DNM1L.
Abstract PRKAA (protein kinase, AMP-activated, α catalytic subunit) regulates mitochondrial biogenesis, function, and turnover. However, the molecular mechanisms by which PRKAA regulates mitochondrial dynamics remain poorly characterized. Here, we report that PRKAA regulated mitochondrial fission via the autophagy-dependent degradation of DNM1L (dynamin 1-like). Deletion of Prkaa1/AMPKα1 or Prkaa2/AMPKα2 resulted in defective autophagy, DNM1L accumulation, and aberrant mitochondrial fragmentation in the mouse aortic endothelium. Furthermore, autophagy inhibition by chloroquine treatment or ATG7 small interferin...
Source: Autophagy - January 12, 2017 Category: Cytology Authors: Wang Q, Wu S, Zhu H, Ding Y, Dai X, Ouyang C, Han YM, Xie Z, Zou MH Tags: Autophagy Source Type: research

ER-Mitochondria signaling regulates autophagy.
Abstract The endoplasmic reticulum (ER) and mitochondria form tight functional contacts that regulate a number of key cellular processes. The formation of these contacts involves "tethering proteins" that function to recruit regions of ER to mitochondria. The integral ER protein VAPB (VAMP associated protein B and C) binds to the outer mitochondrial membrane protein, RMDN3/PTPIP51 (regulator of microtubule dynamics 3) to form one such set of tethers. Recently, we showed that the VAPB-RMDN3 tethers regulate macroautophagy/autophagy. Small interfering RNA (siRNA) knockdown of VAPB or RMDN3 to loosen ER-mitochondria ...
Source: Autophagy - May 26, 2017 Category: Cytology Authors: Gomez-Suaga P, Paillusson S, Miller CCJ Tags: Autophagy Source Type: research

Thyroid hormone (T3) stimulates brown adipose tissue activation via mitochondrial biogenesis and MTOR-mediated mitophagy.
Abstract The thyroid hormone triiodothyronine (T3) activates thermogenesis by uncoupling electron transport from ATP synthesis in brown adipose tissue (BAT) mitochondria. Although T3 can induce thermogenesis by sympathetic innervation, little is known about its cell autonomous effects on BAT mitochondria. We thus examined effects of T3 on mitochondrial activity, autophagy, and metabolism in primary brown adipocytes and BAT and found that T3 increased fatty acid oxidation and mitochondrial respiration as well as autophagic flux, mitophagy, and mitochondrial biogenesis. Interestingly, there was no significant induct...
Source: Autophagy - September 13, 2018 Category: Cytology Authors: Yau WW, Singh BK, Lesmana R, Zhou J, Sinha RA, Wong KA, Wu Y, Bay BH, Sugii S, Sun L, Yen PM Tags: Autophagy Source Type: research

Autophagy drives fibroblast senescence through MTORC2 regulation.
Abstract Sustained macroautophagy/autophagy favors the differentiation of fibroblasts into myofibroblasts. Cellular senescence, another means of responding to long-term cellular stress, has also been linked to myofibroblast differentiation and fibrosis. Here, we evaluate the relationship between senescence and myofibroblast differentiation in the context of sustained autophagy. We analyzed markers of cell cycle arrest/senescence in fibroblasts in vitro, where autophagy was triggered by serum starvation (SS). Autophagic fibroblasts expressed the senescence biomarkers CDKN1A/p21 and CDKN2A/p16 and exhibited increase...
Source: Autophagy - January 12, 2020 Category: Cytology Authors: Bernard M, Yang B, Migneault F, Turgeon J, Dieudé M, Olivier MA, Cardin GB, El-Diwany M, Underwood K, Rodier F, Hébert MJ Tags: Autophagy Source Type: research

Increased alveolar epithelial TRAF6 via autophagy-dependent TRIM37 degradation mediates particulate matter-induced lung metastasis
Autophagy. 2021 Sep 15:1-19. doi: 10.1080/15548627.2021.1965421. Online ahead of print.ABSTRACTEpidemiological and clinical studies have shown that exposure to particulate matter (PM) is associated with an increased incidence of lung cancer and metastasis. However, the underlying mechanism remains unclear. Here, we demonstrated the central role of PM-induced neutrophil recruitment in promoting lung cancer metastasis. We found that reactive oxygen species (ROS)-mediated alveolar epithelial macroautophagy/autophagy was essential for initiating neutrophil chemotaxis and pre-metastatic niche formation in the lungs in response ...
Source: Autophagy - September 15, 2021 Category: Cytology Authors: Jiajun Liu Shumin Li Xuefeng Fei Xi Nan Yingying Shen Huiqing Xiu Stephania A Cormier Chaojie Lu Chuqi Guo Shibo Wang Zhijian Cai Pingli Wang Source Type: research

High-resolution visualization and assessment of basal and OXPHOS-induced mitophagy in H9c2 cardiomyoblasts
In this study, we visualized and assessed the level of mitophagy in H9c2 cardiomyoblasts at basal conditions and after OXPHOS induction by galactose adaptation. We used cells with a stable expression of a pH-sensitive fluorescent mitochondrial reporter and applied state-of-the-art imaging techniques and image analysis. Our data showed a significant increase in acidic mitochondria after galactose adaptation. Using a machine-learning approach we also demonstrated increased mitochondrial fragmentation by OXPHOS induction. Furthermore, super-resolution microscopy of live cells enabled capturing of mitochondrial fragments withi...
Source: Autophagy - July 5, 2023 Category: Cytology Authors: Gustav Godtliebsen Kenneth Bowitz Larsen Zambarlal Bhujabal Ida S Opstad Mireia Nager Abhinanda R Punnakkal Trine B Kalstad Randi Olsen Trine Lund Dilip K Prasad Krishna Agarwal Truls Myrmel Asa Birna Birgisdottir Source Type: research