Filtered By:
Source: Autophagy

This page shows you your search results in order of date. This is page number 7.

Order by Relevance | Date

Total 127 results found since Jan 2013.

Redundancy of human ATG4 protease isoforms in autophagy and LC3/GABARAP processing revealed in cells.
Abstract Macroautophagy/autophagy is a cellular degradation pathway that delivers cytoplasmic material to lysosomes via double-membrane organelles called autophagosomes. Lipidation of ubiquitin-like LC3/GABARAP proteins on the autophagosome membrane is important for autophagy. The cysteine protease ATG4 executes 2 LC3/GABARAP processing events: priming of newly synthesized pro-LC3/GABARAP to enable subsequent lipidation, and delipidation/deconjugation of lipidated LC3/GABARAP (the exact purpose of which is unclear in mammals). Four ATG4 isoforms (ATG4A to ATG4D) exist in mammals; however, the functional redundancy...
Source: Autophagy - January 21, 2019 Category: Cytology Authors: Agrotis A, Pengo N, Burden JJ, Ketteler R 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

Activation of ferritinophagy is required for the RNA-binding protein ELAVL1/HuR to regulate ferroptosis in hepatic stellate cells.
In this study, we report that the RNA-binding protein ELAVL1/HuR plays a crucial role in regulating ferroptosis in liver fibrosis. Upon exposure to ferroptosis-inducing compounds, ELAVL1 protein expression was remarkably increased through the inhibition of the ubiquitin-proteasome pathway. ELAVL1 siRNA led to ferroptosis resistance, whereas ELAVL1 plasmid contributed to classical ferroptotic events. Interestingly, upregulated ELAVL1 expression also appeared to increase autophagosome generation and macroautophagic/autophagic flux, which was the underlying mechanism for ELAVL1-enhanced ferroptosis. Autophagy depletion comple...
Source: Autophagy - August 6, 2018 Category: Cytology Authors: Zhang Z, Yao Z, Wang L, Ding H, Shao J, Chen A, Zhang F, Zheng S Tags: Autophagy Source Type: research

The anti-apoptotic ubiquitin conjugating enzyme BIRC6/BRUCE regulates autophagosome-lysosome fusion.
Abstract The Inhibitor of Apoptosis (IAP) family member, BIRC6/BRUCE is a ubiquitin conjugating E2 enzyme and a well-established anti-apoptosis regulator. However, its role in mammalian autophagy has not been shown. We identified BIRC6 as an important positive regulator of macroautophagy/autophagy by performing an siRNA screen targeting enzymes in the ubiquitin pathway. Compared to wild-type cells, BIRC6-deficient cells show accumulation of lipidated LC3B both at basal and starved conditions. Furthermore, BIRC6 deficiency blocks starvation-induced autophagic flux monitored by a tandem fluorescent autophagy sensor,...
Source: Autophagy - June 21, 2018 Category: Cytology Authors: Ikeda F Tags: Autophagy Source Type: research

The Exoribonuclease Xrn1 Is a Post-Transcriptional Negative Regulator of Autophagy.
Abstract Macroautophagy/autophagy is a conserved catabolic process that promotes survival during stress. Autophagic dysfunction is associated with pathologies such as cancer and neurodegenerative diseases. Thus, autophagy must be strictly modulated at multiple levels (transcriptional, post-transcriptional, translational and post-translational) to prevent deregulation. Relatively little is known about the post-transcriptional control of autophagy. Here we report that the exoribonuclease Xrn1/XRN1 functions as a negative autophagy factor in the yeast Saccharomyces cerevisiae and in mammalian cells. In yeast, chromos...
Source: Autophagy - February 21, 2018 Category: Cytology Authors: Delorme-Axford E, Abernathy E, Lennemann NJ, Bernard A, Ariosa A, Coyne CB, Kirkegaard K, Klionsky DJ Tags: Autophagy Source Type: research

HEPES activates a MiT/TFE-dependent lysosomal-autophagic gene network in cultured cells: A call for caution.
Abstract In recent years, the lysosome has emerged as a highly dynamic, transcriptionally regulated organelle that is integral to nutrient-sensing and metabolic rewiring. This is coordinated by a lysosome-to-nucleus signaling nexus in which MTORC1 controls the subcellular distribution of the microphthalmia-transcription factor E (MiT/TFE) family of "master lysosomal regulators". Yet, despite the importance of the lysosome in cellular metabolism, the impact of traditional in vitro culture media on lysosomal dynamics and/or MiT/TFE localization has not been fully appreciated. Here, we identify HEPES, a chemical buff...
Source: Autophagy - February 17, 2018 Category: Cytology Authors: Tol MJ, van der Lienden MJC, Gabriel TL, Hagen JJ, Scheij S, Veenendaal T, Klumperman J, Donker-Koopman WE, Verhoeven AJ, Overkleeft H, Aerts JM, Argmann CA, van Eijk M Tags: Autophagy Source Type: research

Engagement of circular RNA HECW2 in the nonautophagic role of ATG5 implicated in the endothelial-mesenchymal transition.
Abstract Endothelial-mesenchymal transition (EndoMT) is associated with damage to blood-brain barrier (BBB) integrity. Circular RNAs (circRNAs) are highly expressed in the brain and are involved in brain diseases; however, whether circRNAs regulate the EndoMT in the brain remains unknown. Our study demonstrated that circHECW2 regulated the EndoMT by directly binding to MIR30D, a significantly downregulated miRNA from miRNA profiling, which subsequently caused an increased expression of ATG5. These findings shed new light on the understanding of the noncanonical role of ATG5 in the EndoMT induced by methamphetamine...
Source: Autophagy - December 20, 2017 Category: Cytology Authors: Yang L, Han B, Zhang Y, Bai Y, Chao J, Hu G, Yao H Tags: Autophagy Source Type: research

Phosphoproteome-based kinase activity profiling reveals the critical role of MAP2K2 and PLK1 in neuronal autophagy.
In this study, quantitative phosphoproteomic profiling together with a computational analysis was performed to delineate the phosphorylation signalling networks regulated by 2 natural neuroprotective autophagy enhancers, corynoxine (Cory) and corynoxine B (Cory B). To identify key regulators, namely, protein kinases, we developed a novel network-based algorithm of in silico Kinome Activity Profiling (iKAP) to computationally infer potentially important protein kinases from phosphorylation networks. Using this algorithm, we observed that Cory or Cory B potentially regulated several kinases. We predicted and validated that C...
Source: Autophagy - September 21, 2017 Category: Cytology Authors: Chen LL, Wang YB, Song JX, Deng WK, Lu JH, Ma LL, Yang CB, Li M, Xue Y Tags: Autophagy Source Type: research

Circular RNA HIPK2 regulates astrocyte activation via cooperation of autophagy and ER stress by targeting MIR124-2HG.
Abstract Circular RNAs are a subclass of noncoding RNAs in mammalian cells; however, whether these RNAs are involved in the regulation of astrocyte activation is largely unknown. Here, we have shown that the circular RNA HIPK2 (circHIPK2) functions as an endogenous microRNA-124 (MIR124-2HG) sponge to sequester MIR124-2HG and inhibit its activity, resulting in increased sigma non-opioid intracellular receptor 1 (SIGMAR1/OPRS1) expression. Knockdown of circHIPK2 expression significantly inhibited astrocyte activation via the regulation of autophagy and endoplasmic reticulum (ER) stress through the targeting of MIR12...
Source: Autophagy - August 8, 2017 Category: Cytology Authors: Huang R, Zhang Y, Han B, Bai Y, Zhou R, Gan G, Chao J, Hu G, Yao H 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

Targeting AMPK-ULK1-mediated autophagy for combating BET inhibitor resistance in acute myeloid leukemia stem cells.
In this study, we evaluated the mechanisms underlying LSC resistance to the BET inhibitor JQ1. We evaluated the levels of apoptosis and macroautophagy/autophagy induced by JQ1 in LSC-like leukemia cell lines and primary CD34(+) CD38(-) leukemic blasts obtained from AML cases with normal karyotype without recurrent mutations. JQ1 effectively induced apoptosis in a concentration-dependent manner in JQ1-sensitive AML cells. However, in JQ1-resistant AML LSCs, JQ1 induced little apoptosis and led to upregulation of BECN1/beclin-1, increased LC3 lipidation, formation of autophagosomes, and downregulation of SQSTM1/p62. Inhibiti...
Source: Autophagy - January 23, 2017 Category: Cytology Authors: Jang JE, Eom JI, Jeung HK, Cheong JW, Lee JY, Kim JS, Min YH Tags: Autophagy Source Type: research

PTK2-mediated degradation of ATG3 impedes cancer cells susceptible to DNA damage treatment.
Abstract ATG3 (autophagy related 3) is an E2-like enzyme essential for autophagy; however, it is unknown whether it has an autophagy-independent function. Here, we report that ATG3 is a relatively stable protein in unstressed cells, but it is degraded in response to DNA-damaging agents such as etoposide or cisplatin. With mass spectrometry and a mutagenesis assay, phosphorylation of tyrosine 203 of ATG3 was identified to be a critical modification for its degradation, which was further confirmed by manipulating ATG3(Y203E) (phosphorylation mimic) or ATG3(Y203F) (phosphorylation-incompetent) in Atg3 knockout MEFs. ...
Source: Autophagy - January 18, 2017 Category: Cytology Authors: Ma K, Fu W, Tang M, Zhang C, Hou T, Li R, Lu X, Wang Y, Zhou J, Li X, Zhang L, Wang L, Zhao Y, Zhu WG 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

SNAPIN is critical for lysosomal acidification and autophagosome maturation in macrophages.
Abstract We previously observed that SNAPIN, which is an adaptor protein in the SNARE core complex, was highly expressed in rheumatoid arthritis synovial tissue macrophages, but its role in macrophages and autoimmunity is unknown. To identify SNAPIN's role in these cells, we employed siRNA to silence the expression of SNAPIN in primary human macrophages. Silencing SNAPIN resulted in swollen lysosomes with impaired CTSD (cathepsin D) activation, although total CTSD was not reduced. Neither endosome cargo delivery nor lysosomal fusion with endosomes or autophagosomes was inhibited following the forced silencing of S...
Source: Autophagy - December 7, 2016 Category: Cytology Authors: Shi B, Huang QQ, Birkett R, Doyle R, Dorfleutner A, Stehlik C, He C, Pope RM Tags: Autophagy Source Type: research

Ehrlichia secretes Etf-1 to induce autophagy and capture nutrients for its growth through RAB5 and class III phosphatidylinositol 3-kinase.
Abstract Ehrlichia chaffeensis is an obligatory intracellular bacterium that causes a potentially fatal emerging zoonosis, human monocytic ehrlichiosis. E. chaffeensis has a limited capacity for biosynthesis and metabolism and thus depends mostly on host-synthesized nutrients for growth. Although the host cell cytoplasm is rich with these nutrients, as E. chaffeensis is confined within the early endosome-like membrane-bound compartment, only host nutrients that enter the compartment can be used by this bacterium. How this occurs is unknown. We found that ehrlichial replication depended on autophagy induction invol...
Source: Autophagy - October 31, 2016 Category: Cytology Authors: Lin M, Liu H, Xiong Q, Niu H, Cheng Z, Yamamoto A, Rikihisa Y Tags: Autophagy Source Type: research