Redox activation of ATM enhances GSNOR translation to sustain mitophagy and tolerance to oxidative stress.

Abstract:

:The denitrosylase S-nitrosoglutathione reductase (GSNOR) has been suggested to sustain mitochondrial removal by autophagy (mitophagy), functionally linking S-nitrosylation to cell senescence and aging. In this study, we provide evidence that GSNOR is induced at the translational level in response to hydrogen peroxide and mitochondrial ROS. The use of selective pharmacological inhibitors and siRNA demonstrates that GSNOR induction is an event downstream of the redox-mediated activation of ATM, which in turn phosphorylates and activates CHK2 and p53 as intermediate players of this signaling cascade. The modulation of ATM/GSNOR axis, or the expression of a redox-insensitive ATM mutant influences cell sensitivity to nitrosative and oxidative stress, impairs mitophagy and affects cell survival. Remarkably, this interplay modulates T-cell activation, supporting the conclusion that GSNOR is a key molecular effector of the antioxidant function of ATM and providing new clues to comprehend the pleiotropic effects of ATM in the context of immune function.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Cirotti C,Rizza S,Giglio P,Poerio N,Allega MF,Claps G,Pecorari C,Lee JH,Benassi B,Barilà D,Robert C,Stamler JS,Cecconi F,Fraziano M,Paull TT,Filomeni G

doi

10.15252/embr.202050500

subject

Has Abstract

pub_date

2020-11-27 00:00:00

pages

e50500

eissn

1469-221X

issn

1469-3178

pub_type

杂志文章
  • The evolution of human endurance: Research on the biology of extreme endurance gives insights into its evolution in humans and animals.

    abstract::Research into the extreme feats of endurance that humans and some animals achieve has uncovered a range of metabolic and physiological adaptations along with their evolutionary origins. ...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审

    doi:10.15252/embr.201949396

    authors: Hunter P

    更新日期:2019-11-05 00:00:00

  • Monitoring agonist-promoted conformational changes of beta-arrestin in living cells by intramolecular BRET.

    abstract::Recruitment of beta-arrestin (beta-arr) to agonist-stimulated G-protein-coupled receptors (GPCRs) has a crucial role in controlling signalling efficacy and selectivity. When translocated to the receptor, beta-arr is believed to undergo important conformational rearrangement necessary for its downstream actions. To pro...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.7400373

    authors: Charest PG,Terrillon S,Bouvier M

    更新日期:2005-04-01 00:00:00

  • A selective PIKfyve inhibitor blocks PtdIns(3,5)P(2) production and disrupts endomembrane transport and retroviral budding.

    abstract::Phosphoinositides have crucial roles in cellular controls, many of which have been established through the use of small-molecule inhibitors. Here, we describe YM201636, a potent inhibitor of the mammalian class III phosphatidylinositol phosphate kinase PIKfyve, which synthesizes phosphatidylinositol 3,5-bisphosphate. ...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.7401155

    authors: Jefferies HB,Cooke FT,Jat P,Boucheron C,Koizumi T,Hayakawa M,Kaizawa H,Ohishi T,Workman P,Waterfield MD,Parker PJ

    更新日期:2008-02-01 00:00:00

  • Two internal ribosome entry sites mediate the translation of p53 isoforms.

    abstract::The p53 tumour suppressor protein has a crucial role in cell-cycle arrest and apoptosis. Previous reports show that the p53 messenger RNA is translated to produce an amino-terminal-deleted isoform (DeltaN-p53) from an internal initiation codon, which acts as a dominant-negative inhibitor of full-length p53. Here, we s...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.7400623

    authors: Ray PS,Grover R,Das S

    更新日期:2006-04-01 00:00:00

  • Conditional gene knock-down by CRE-dependent short interfering RNAs.

    abstract::Short interfering RNAs (siRNAs) are short (21-23 nt) double-stranded RNAs that direct the sequence-specific degradation of corresponding mRNAs, resulting in suppression of gene activity. siRNAs are powerful tools for gene functional analysis in mammals. Chemically synthesized siRNAs permit transient gene repression bu...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.7400064

    authors: Fritsch L,Martinez LA,Sekhri R,Naguibneva I,Gérard M,Vandromme M,Schaeffer L,Harel-Bellan A

    更新日期:2004-02-01 00:00:00

  • The Gam protein of bacteriophage Mu is an orthologue of eukaryotic Ku.

    abstract::Mu bacteriophage inserts its DNA into the genome of host bacteria and is used as a model for DNA transposition events in other systems. The eukaryotic Ku protein has key roles in DNA repair and in certain transposition events. Here we show that the Gam protein of phage Mu is conserved in bacteria, has sequence homolog...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.embor709

    authors: d'Adda di Fagagna F,Weller GR,Doherty AJ,Jackson SP

    更新日期:2003-01-01 00:00:00

  • Resistance of glia-like central and peripheral neural stem cells to genetically induced mitochondrial dysfunction--differential effects on neurogenesis.

    abstract::Mitochondria play a central role in stem cell homeostasis. Reversible switching between aerobic and anaerobic metabolism is critical for stem cell quiescence, multipotency, and differentiation, as well as for cell reprogramming. However, the effect of mitochondrial dysfunction on neural stem cell (NSC) function is uns...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201540982

    authors: Díaz-Castro B,Pardal R,García-Flores P,Sobrino V,Durán R,Piruat JI,López-Barneo J

    更新日期:2015-11-01 00:00:00

  • Effect of CpG methylation on RAG1/RAG2 reactivity: implications of direct and indirect mechanisms for controlling V(D)J cleavage.

    abstract::It has been suggested that DNA methylation/demethylation is involved in regulating V(D)J rearrangement. Although methylated DNA is thought to induce an inaccessible chromatin structure, it is unclear whether DNA methylation can directly control V(D)J recombination independently of chromatin structure. In this study, w...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.embor904

    authors: Nakase H,Takahama Y,Akamatsu Y

    更新日期:2003-08-01 00:00:00

  • Distinct germline progenitor subsets defined through Tsc2-mTORC1 signaling.

    abstract::Adult tissue maintenance is often dependent on resident stem cells; however, the phenotypic and functional heterogeneity existing within this self-renewing population is poorly understood. Here, we define distinct subsets of undifferentiated spermatogonia (spermatogonial progenitor cells; SPCs) by differential respons...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201439379

    authors: Hobbs RM,La HM,Mäkelä JA,Kobayashi T,Noda T,Pandolfi PP

    更新日期:2015-04-01 00:00:00

  • Requirements of peptidoglycan structure that allow detection by the Drosophila Toll pathway.

    abstract::The Drosophila immune system is able to discriminate between classes of bacteria. Detection of Gram-positive bacteria involves a complex of two pattern recognition receptors: peptidoglycan recognition protein SA (PGRP-SA) and Gram-negative binding protein 1 (GNBP1). These activate the Toll signalling pathway. To defin...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.7400371

    authors: Filipe SR,Tomasz A,Ligoxygakis P

    更新日期:2005-04-01 00:00:00

  • AKT-dependent phosphorylation of Niban regulates nucleophosmin- and MDM2-mediated p53 stability and cell apoptosis.

    abstract::Although Niban is highly expressed in human cancer cells, the cellular functions of Niban remain largely unknown. We demonstrate here that ultraviolet irradiation induces phosphorylation of Niban at S602 by AKT, which increases the association of Niban with nucleophosmin and disassociation of nucleophosmin from the MD...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/embor.2012.53

    authors: Ji H,Ding Z,Hawke D,Xing D,Jiang BH,Mills GB,Lu Z

    更新日期:2012-06-01 00:00:00

  • COVID-19 and the boundaries of open science and innovation: Lessons of traceability from genomic data sharing and biosecurity.

    abstract::The COVID-19 crisis has further highlighted the challenges for open science and data sharing in biomedical research and the need for more traceability and transparency. ...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.202051773

    authors: Minari J,Yoshizawa G,Shinomiya N

    更新日期:2020-11-05 00:00:00

  • Tpz1TPP1 SUMOylation reveals evolutionary conservation of SUMO-dependent Stn1 telomere association.

    abstract::Elongation of the telomeric overhang by telomerase is counteracted by synthesis of the complementary strand by the CST complex, CTC1(Cdc13)/Stn1/Ten1. Interaction of budding yeast Stn1 with overhang-binding Cdc13 is increased by Cdc13 SUMOylation. Human and fission yeast CST instead interact with overhang-binding TPP1...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201438919

    authors: Garg M,Gurung RL,Mansoubi S,Ahmed JO,Davé A,Watts FZ,Bianchi A

    更新日期:2014-08-01 00:00:00

  • The 3.7 A projection map of the glycerol facilitator GlpF: a variant of the aquaporin tetramer.

    abstract::GlpF, the glycerol facilitator protein of Escherichia coli, is an archetypal member of the aquaporin superfamily. To assess its structure, recombinant histidine-tagged protein was overexpressed, solubilized in octylglucoside and purified to homogeneity. Negative stain electron microscopy of solubilized GlpF protein re...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvd022

    authors: Braun T,Philippsen A,Wirtz S,Borgnia MJ,Agre P,Kühlbrandt W,Engel A,Stahlberg H

    更新日期:2000-08-01 00:00:00

  • Helicase89B is a Mot1p/BTAF1 homologue that mediates an antimicrobial response in Drosophila.

    abstract::We have identified a novel component, Helicase89B, that is required for the inducible antimicrobial response in Drosophila larvae by means of a P-element insertional genetic screen. Helicase89B belongs to the Mot1p/BTAF1 subfamily of SNF2-like ATPases. This subfamily can interact with TATA-binding proteins, but whethe...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.7400542

    authors: Yagi Y,Ip YT

    更新日期:2005-11-01 00:00:00

  • Do scientists read enough fiction?

    abstract::Reading the academic literature is an essential part of a scientist's job. David Smith argues that reading fiction can be even more important for creativity and productivity than papers and reviews. ...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.202052206

    authors: Smith DR

    更新日期:2021-01-04 00:00:00

  • Human METTL16 is a N6-methyladenosine (m6A) methyltransferase that targets pre-mRNAs and various non-coding RNAs.

    abstract::N6-methyladenosine (m6A) is a highly dynamic RNA modification that has recently emerged as a key regulator of gene expression. While many m6A modifications are installed by the METTL3-METTL14 complex, others appear to be introduced independently, implying that additional human m6A methyltransferases remain to be ident...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201744940

    authors: Warda AS,Kretschmer J,Hackert P,Lenz C,Urlaub H,Höbartner C,Sloan KE,Bohnsack MT

    更新日期:2017-11-01 00:00:00

  • Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex.

    abstract::Histone deacetylases (HDACs)-an enzyme family that deacetylates histones and non-histone proteins-are implicated in human diseases such as cancer, and the first-generation of HDAC inhibitors are now in clinical trials. Here, we report the 2.0 A resolution crystal structure of a catalytically inactive HDAC8 active-site...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.7401047

    authors: Vannini A,Volpari C,Gallinari P,Jones P,Mattu M,Carfí A,De Francesco R,Steinkühler C,Di Marco S

    更新日期:2007-09-01 00:00:00

  • Translation acrobatics: how cancer cells exploit alternate modes of translational initiation.

    abstract::Recent work has brought to light many different mechanisms of translation initiation that function in cells in parallel to canonical cap-dependent initiation. This has important implications for cancer. Canonical cap-dependent translation initiation is inhibited by many stresses such as hypoxia, nutrient limitation, p...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审

    doi:10.15252/embr.201845947

    authors: Sriram A,Bohlen J,Teleman AA

    更新日期:2018-10-01 00:00:00

  • Involvement of state transitions in the switch between linear and cyclic electron flow in Chlamydomonas reinhardtii.

    abstract::The energetic metabolism of photosynthetic organisms is profoundly influenced by state transitions and cyclic electron flow around photosystem I. The former involve a reversible redistribution of the light-harvesting antenna between photosystem I and photosystem II and optimize light energy utilization in photosynthes...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvf047

    authors: Finazzi G,Rappaport F,Furia A,Fleischmann M,Rochaix JD,Zito F,Forti G

    更新日期:2002-03-01 00:00:00

  • Control of epidermal growth factor receptor endocytosis by receptor dimerization, rather than receptor kinase activation.

    abstract::Given that ligand binding is essential for the rapid internalization of epidermal growth factor receptor (EGFR), the events induced by ligand binding probably contribute to the regulation of EGFR internalization. These events include receptor dimerization, activation of intrinsic tyrosine kinase activity and autophosp...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.7400491

    authors: Wang Q,Villeneuve G,Wang Z

    更新日期:2005-10-01 00:00:00

  • Mitochondrial permeability transition involves dissociation of F1FO ATP synthase dimers and C-ring conformation.

    abstract::The impact of the mitochondrial permeability transition (MPT) on cellular physiology is well characterized. In contrast, the composition and mode of action of the permeability transition pore complex (PTPC), the supramolecular entity that initiates MPT, remain to be elucidated. Specifically, the precise contribution o...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201643602

    authors: Bonora M,Morganti C,Morciano G,Pedriali G,Lebiedzinska-Arciszewska M,Aquila G,Giorgi C,Rizzo P,Campo G,Ferrari R,Kroemer G,Wieckowski MR,Galluzzi L,Pinton P

    更新日期:2017-07-01 00:00:00

  • PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation.

    abstract::Autophagosome formation is promoted by the PI3 kinase complex and negatively regulated by myotubularin phosphatases, indicating that regulation of local phosphatidylinositol 3-phosphate (PtdIns3P) levels is important for this early phase of autophagy. Here, we show that the Caenorhabditis elegans myotubularin phosphat...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201438618

    authors: Wu Y,Cheng S,Zhao H,Zou W,Yoshina S,Mitani S,Zhang H,Wang X

    更新日期:2014-09-01 00:00:00

  • A novel muscle LIM-only protein is generated from the paxillin gene locus in Drosophila.

    abstract::Paxillin is a protein containing four LIM domains, and functions in integrin signaling. We report here that two transcripts are generated from the paxillin gene locus in Drosophila; one encodes a protein homolog of the vertebrate Paxillin (DPxn37), and the other a protein with only three LIM domains, partly encoded by...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kve178

    authors: Yagi R,Ishimaru S,Yano H,Gaul U,Hanafusa H,Sabe H

    更新日期:2001-09-01 00:00:00

  • COP9 signalosome controls the Carma1-Bcl10-Malt1 complex upon T-cell stimulation.

    abstract::The Carma1-Bcl10-Malt1 (CBM) complex connects T-cell receptor (TCR) signalling to the canonical IkappaB kinase (IKK)/NF (nuclear factor)-kappaB pathway. Earlier studies have indicated that the COP9 signalosome (CSN), a pleiotropic regulator of the ubiquitin/26S proteasome system, controls antigen responses in T cells....

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/embor.2009.64

    authors: Welteke V,Eitelhuber A,Düwel M,Schweitzer K,Naumann M,Krappmann D

    更新日期:2009-06-01 00:00:00

  • Processive kinesins require loose mechanical coupling for efficient collective motility.

    abstract::Processive motor proteins are stochastic steppers that perform actual mechanical steps for only a minor fraction of the time they are bound to the filament track. Motors usually work in teams and therefore the question arises whether the stochasticity of stepping can cause mutual interference when motors are mechanica...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/embor.2008.169

    authors: Bieling P,Telley IA,Piehler J,Surrey T

    更新日期:2008-11-01 00:00:00

  • The Methanobacterium thermoautotrophicum MCM protein can form heptameric rings.

    abstract::Mini-chromosome maintenance (MCM) proteins form a conserved family found in all eukaryotes and are essential for DNA replication. They exist as heteromultimeric complexes containing as many as six different proteins. These complexes are believed to be the replicative helicases, functioning as hexameric rings at replic...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvf160

    authors: Yu X,VanLoock MS,Poplawski A,Kelman Z,Xiang T,Tye BK,Egelman EH

    更新日期:2002-08-01 00:00:00

  • Structural coupling of the EF hand and C-terminal GTPase domains in the mitochondrial protein Miro.

    abstract::Miro is a highly conserved calcium-binding GTPase at the regulatory nexus of mitochondrial transport and autophagy. Here we present crystal structures comprising the tandem EF hand and carboxy terminal GTPase (cGTPase) domains of Drosophila Miro. The structures reveal two previously unidentified 'hidden' EF hands, eac...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/embor.2013.151

    authors: Klosowiak JL,Focia PJ,Chakravarthy S,Landahl EC,Freymann DM,Rice SE

    更新日期:2013-11-01 00:00:00

  • Mps1 promotes rapid centromere accumulation of Aurora B.

    abstract::Aurora B localization to mitotic centromeres, which is required for proper chromosome alignment during mitosis, relies on Haspin-dependent histone H3 phosphorylation and on Bub1-dependent histone H2A phosphorylation--which interacts with Borealin through a Shugoshin (Sgo) intermediate. We demonstrate that Mps1 stimula...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/embor.2012.93

    authors: van der Waal MS,Saurin AT,Vromans MJ,Vleugel M,Wurzenberger C,Gerlich DW,Medema RH,Kops GJ,Lens SM

    更新日期:2012-09-01 00:00:00

  • NAD(P) transhydrogenase has vital non-mitochondrial functions in malaria parasite transmission.

    abstract::Nicotinamide adenine dinucleotide (NAD) and its phosphorylated form (NADP) are vital for cell function in all organisms and form cofactors to a host of enzymes in catabolic and anabolic processes. NAD(P) transhydrogenases (NTHs) catalyse hydride ion transfer between NAD(H) and NADP(H). Membrane-bound NTH isoforms resi...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201947832

    authors: Saeed S,Tremp AZ,Sharma V,Lasonder E,Dessens JT

    更新日期:2020-03-04 00:00:00