{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T21:07:56Z","timestamp":1776373676355,"version":"3.51.2"},"update-to":[{"DOI":"10.1371\/journal.pbio.3002720","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T00:00:00Z","timestamp":1721692800000}}],"reference-count":92,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012207","name":"Grace Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012207","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM142728"],"award-info":[{"award-number":["R35GM142728"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG16636"],"award-info":[{"award-number":["R01AG16636"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>The conserved SKN-1A\/Nrf1 transcription factor regulates the expression of proteasome subunit genes and is essential for maintenance of adequate proteasome function in animal development, aging, and stress responses. Unusual among transcription factors, SKN-1A\/Nrf1 is a glycoprotein synthesized in the endoplasmic reticulum (ER). N-glycosylated SKN-1A\/Nrf1 exits the ER and is deglycosylated in the cytosol by the PNG-1\/NGLY1 peptide:N-glycanase. Deglycosylation edits the protein sequence of SKN-1A\/Nrf1 by converting N-glycosylated asparagine residues to aspartate, which is necessary for SKN-1A\/Nrf1 transcriptional activation of proteasome subunit genes. Homozygous loss-of-function mutations in the peptide:N-glycanase (NGLY1) gene cause NGLY1 deficiency, a congenital disorder of deglycosylation. There are no effective treatments for NGLY1 deficiency. Since SKN-1A\/Nrf1 is a major client of NGLY1, the resulting proteasome deficit contributes to NGLY1 disease. We sought to identify targets for mitigation of proteasome dysfunction in NGLY1 deficiency that might indicate new avenues for treatment. We isolated mutations that suppress the sensitivity to proteasome inhibitors caused by inactivation of the NGLY1 ortholog PNG-1 in <jats:italic>Caenorhabditis elegans<\/jats:italic>. We identified multiple suppressor mutations affecting 3 conserved genes: <jats:italic>rsks-1<\/jats:italic>, <jats:italic>tald-1<\/jats:italic>, and <jats:italic>ent-4<\/jats:italic>. We show that the suppressors act through a SKN-1\/Nrf-independent mechanism and confer proteostasis benefits consistent with amelioration of proteasome dysfunction. <jats:italic>ent-4<\/jats:italic> encodes an intestinal nucleoside\/nucleotide transporter, and we show that restriction of nucleotide availability is beneficial, whereas a nucleotide-rich diet exacerbates proteasome dysfunction in PNG-1\/NGLY1-deficient <jats:italic>C<\/jats:italic>. <jats:italic>elegans<\/jats:italic>. Our findings suggest that dietary or pharmacological interventions altering nucleotide availability have the potential to mitigate proteasome insufficiency in NGLY1 deficiency and other diseases associated with proteasome dysfunction.<\/jats:p>","DOI":"10.1371\/journal.pbio.3002720","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T18:01:01Z","timestamp":1720720861000},"page":"e3002720","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mutations in nucleotide metabolism genes bypass proteasome defects in png-1\/NGLY1-deficient Caenorhabditis elegans"],"prefix":"10.1371","volume":"22","author":[{"given":"Katherine S.","family":"Yanagi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Briar","family":"Jochim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheikh Omar","family":"Kunjo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Breen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Ruvkun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7342-4136","authenticated-orcid":true,"given":"Nicolas","family":"Lehrbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"issue":"5","key":"pbio.3002720.ref001","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.cell.2017.04.023","article-title":"The Logic of the 26S Proteasome.","volume":"169","author":"GA Collins","year":"2017","journal-title":"Cell"},{"key":"pbio.3002720.ref002","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1146\/annurev-biochem-061516-044518","article-title":"Protein Misfolding Diseases","volume":"86","author":"FU Hartl","year":"2017","journal-title":"Annu Rev Biochem"},{"key":"pbio.3002720.ref003","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1146\/annurev-cellbio-111315-125334","article-title":"Coping with Protein Quality Control Failure","volume":"33","author":"E Pilla","year":"2017","journal-title":"Annu Rev Cell Dev Biol"},{"issue":"1","key":"pbio.3002720.ref004","doi-asserted-by":"crossref","first-page":"38","DOI":"10.2174\/138920291501140306113344","article-title":"The Mechanistic Links Between Proteasome Activity, Aging and Age-related Diseases.","volume":"15","author":"I Saez","year":"2014","journal-title":"Curr Genomics"},{"issue":"1","key":"pbio.3002720.ref005","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.molcel.2010.02.029","article-title":"Transcription factor Nrf1 mediates the proteasome recovery pathway after proteasome inhibition in mammalian cells","volume":"38","author":"SK Radhakrishnan","year":"2010","journal-title":"Mol Cell"},{"issue":"1","key":"pbio.3002720.ref006","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.molcel.2010.09.012","article-title":"Proteasomal degradation is transcriptionally controlled by TCF11 via an ERAD-dependent feedback loop","volume":"40","author":"J Steffen","year":"2010","journal-title":"Mol Cell"},{"issue":"6","key":"pbio.3002720.ref007","doi-asserted-by":"crossref","first-page":"e1002119","DOI":"10.1371\/journal.pgen.1002119","article-title":"Specific SKN-1\/Nrf stress responses to perturbations in translation elongation and proteasome activity.","volume":"7","author":"X Li","year":"2011","journal-title":"PLoS Genet."},{"key":"pbio.3002720.ref008","doi-asserted-by":"crossref","first-page":"e17721","DOI":"10.7554\/eLife.17721","article-title":"Proteasome dysfunction triggers activation of SKN-1A\/Nrf1 by the aspartic protease DDI-1.","volume":"5","author":"NJ Lehrbach","year":"2016","journal-title":"Elife"},{"key":"pbio.3002720.ref009","doi-asserted-by":"crossref","first-page":"e44425","DOI":"10.7554\/eLife.44425","article-title":"Endoplasmic reticulum-associated SKN-1A\/Nrf1 mediates a cytoplasmic unfolded protein response and promotes longevity.","volume":"8","author":"NJ Lehrbach","year":"2019","journal-title":"Elife"},{"issue":"2","key":"pbio.3002720.ref010","doi-asserted-by":"crossref","first-page":"e1005823","DOI":"10.1371\/journal.pgen.1005823","article-title":"Graded Proteasome Dysfunction in Caenorhabditis elegans Activates an Adaptive Response Involving the Conserved SKN-1 and ELT-2 Transcription Factors and the Autophagy-Lysosome Pathway.","volume":"12","author":"SA Keith","year":"2016","journal-title":"PLoS Genet."},{"key":"pbio.3002720.ref011","doi-asserted-by":"crossref","first-page":"e01856","DOI":"10.7554\/eLife.01856","article-title":"p97-dependent retrotranslocation and proteolytic processing govern formation of active Nrf1 upon proteasome inhibition.","volume":"3","author":"SK Radhakrishnan","year":"2014","journal-title":"Elife"},{"key":"pbio.3002720.ref012","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1038\/srep02006","article-title":"The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity.","volume":"3","author":"Y Zhang","year":"2013","journal-title":"Sci Rep."},{"issue":"2","key":"pbio.3002720.ref013","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.molcel.2020.05.035","article-title":"DDI2 Is a Ubiquitin-Directed Endoprotease Responsible for Cleavage of Transcription Factor NRF1","volume":"79","author":"AB Dirac-Svejstrup","year":"2020","journal-title":"Mol Cell"},{"key":"pbio.3002720.ref014","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.18357","article-title":"The aspartyl protease DDI2 activates Nrf1 to compensate for proteasome dysfunction.","volume":"5","author":"S Koizumi","year":"2016","journal-title":"Elife"},{"issue":"1","key":"pbio.3002720.ref015","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21010327","article-title":"Disabling the Protease DDI2 Attenuates the Transcriptional Activity of NRF1 and Potentiates Proteasome Inhibitor Cytotoxicity.","volume":"21","author":"A Northrop","year":"2020","journal-title":"Int J Mol Sci."},{"issue":"11","key":"pbio.3002720.ref016","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1021\/acscentsci.7b00224","article-title":"Inhibition of NGLY1 Inactivates the Transcription Factor Nrf1 and Potentiates Proteasome Inhibitor Cytotoxicity.","volume":"3","author":"FM Tomlin","year":"2017","journal-title":"ACS Central Science"},{"issue":"3","key":"pbio.3002720.ref017","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.cell.2019.03.035","article-title":"Protein Sequence Editing of SKN-1A\/Nrf1 by Peptide:N-Glycanase Controls Proteasome Gene Expression","volume":"177","author":"NJ Lehrbach","year":"2019","journal-title":"Cell"},{"issue":"27","key":"pbio.3002720.ref018","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2102902118","article-title":"Loss of peptide:N-glycanase causes proteasome dysfunction mediated by a sugar-recognizing ubiquitin ligase","volume":"118","author":"Y Yoshida","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pbio.3002720.ref019","doi-asserted-by":"crossref","first-page":"eadc8917","DOI":"10.1126\/sciadv.adc8917","article-title":"An antisteatosis response regulated by oleic acid through lipid droplet-mediated ERAD enhancement.","volume":"9","author":"JI Castillo-Quan","year":"2023","journal-title":"Sci Adv."},{"issue":"20","key":"pbio.3002720.ref020","doi-asserted-by":"crossref","first-page":"8408","DOI":"10.1073\/pnas.1019209108","article-title":"Loss of nuclear factor E2-related factor 1 in the brain leads to dysregulation of proteasome gene expression and neurodegeneration","volume":"108","author":"CS Lee","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"pbio.3002720.ref021","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/j.1365-2443.2011.01522.x","article-title":"Central nervous system-specific deletion of transcription factor Nrf1 causes progressive motor neuronal dysfunction","volume":"16","author":"A Kobayashi","year":"2011","journal-title":"Genes Cells"},{"issue":"10","key":"pbio.3002720.ref022","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1093\/hmg\/ddw073","article-title":"A small-molecule Nrf1 and Nrf2 activator mitigates polyglutamine toxicity in spinal and bulbar muscular atrophy","volume":"25","author":"LC Bott","year":"2016","journal-title":"Hum Mol Genet"},{"issue":"18","key":"pbio.3002720.ref023","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.15252\/embj.201593725","article-title":"A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson\u2019s disease","volume":"35","author":"JC Villaescusa","year":"2016","journal-title":"EMBO J"},{"key":"pbio.3002720.ref024","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s12915-014-0094-0","article-title":"Proteotoxic crisis, the ubiquitin-proteasome system, and cancer therapy","volume":"12","author":"RJ Deshaies","year":"2014","journal-title":"BMC Biol"},{"issue":"5","key":"pbio.3002720.ref025","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.cell.2017.01.013","article-title":"Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras","volume":"168","author":"T Wang","year":"2017","journal-title":"Cell"},{"issue":"5","key":"pbio.3002720.ref026","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12051065","article-title":"Nelfinavir Inhibits the TCF11\/Nrf1-Mediated Proteasome Recovery Pathway in Multiple Myeloma.","volume":"12","author":"D Fassmannova","year":"2020","journal-title":"Cancers (Basel)."},{"key":"pbio.3002720.ref027","doi-asserted-by":"crossref","first-page":"109775","DOI":"10.1016\/j.cellsig.2020.109775","article-title":"Nelfinavir inhibits human DDI2 and potentiates cytotoxicity of proteasome inhibitors","volume":"75","author":"Y Gu","year":"2020","journal-title":"Cell Signal"},{"issue":"10","key":"pbio.3002720.ref028","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/gim.2014.22","article-title":"Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway","volume":"16","author":"GM Enns","year":"2014","journal-title":"Genet Med"},{"issue":"2","key":"pbio.3002720.ref029","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/gim.2016.75","article-title":"Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation","volume":"19","author":"C Lam","year":"2017","journal-title":"Genet Med"},{"issue":"5","key":"pbio.3002720.ref030","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1093\/emboj\/cdg107","article-title":"A role for N-glycanase in the cytosolic turnover of glycoproteins","volume":"22","author":"C Hirsch","year":"2003","journal-title":"EMBO J"},{"issue":"19","key":"pbio.3002720.ref031","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1042\/BCJ20160453","article-title":"Identification of PNGase-dependent ERAD substrates in Saccharomyces cerevisiae","volume":"473","author":"A Hosomi","year":"2016","journal-title":"Biochem J"},{"issue":"6","key":"pbio.3002720.ref032","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1093\/hmg\/ddy026","article-title":"Transcriptome and functional analysis in a Drosophila model of NGLY1 deficiency provides insight into therapeutic approaches","volume":"27","author":"KG Owings","year":"2018","journal-title":"Hum Mol Genet"},{"issue":"5","key":"pbio.3002720.ref033","first-page":"1585","article-title":"Loss of N-Glycanase 1 Alters Transcriptional and Translational Regulation in K562 Cell Lines G3 (Bethesda).","volume":"10","author":"WF Mueller","year":"2020"},{"issue":"12","key":"pbio.3002720.ref034","doi-asserted-by":"crossref","first-page":"113466","DOI":"10.1016\/j.celrep.2023.113466","article-title":"NGLY1 mutations cause protein aggregation in human neurons","volume":"42","author":"A Manole","year":"2023","journal-title":"Cell Rep"},{"issue":"2","key":"pbio.3002720.ref035","doi-asserted-by":"crossref","first-page":"89","DOI":"10.2183\/pjab.97.005","article-title":"JF1\/B6F1 Ngly1(-\/-) mouse as an isogenic animal model of NGLY1 deficiency.","volume":"97","author":"M Asahina","year":"2021","journal-title":"Proc Jpn Acad Ser B Phys Biol Sci"},{"issue":"10","key":"pbio.3002720.ref036","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1093\/hmg\/ddaa059","article-title":"Ngly1 -\/- rats develop neurodegenerative phenotypes and pathological abnormalities in their peripheral and central nervous systems","volume":"29","author":"M Asahina","year":"2020","journal-title":"Hum Mol Genet"},{"issue":"10","key":"pbio.3002720.ref037","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1084\/jem.20180783","article-title":"N-glycanase NGLY1 regulates mitochondrial homeostasis and inflammation through NRF1","volume":"215","author":"K Yang","year":"2018","journal-title":"J Exp Med"},{"issue":"5","key":"pbio.3002720.ref038","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1523\/JNEUROSCI.4962-08.2010","article-title":"The N-glycanase png-1 acts to limit axon branching during organ formation in Caenorhabditis elegans","volume":"30","author":"N Habibi-Babadi","year":"2010","journal-title":"J Neurosci"},{"issue":"1","key":"pbio.3002720.ref039","doi-asserted-by":"crossref","first-page":"14405","DOI":"10.1038\/s41598-023-41492-9","article-title":"The transcription factor NRF1 (NFE2L1) activates aggrephagy by inducing p62 and GABARAPL1 after proteasome inhibition to maintain proteostasis.","volume":"13","author":"A Hatanaka","year":"2023","journal-title":"Sci Rep."},{"issue":"11","key":"pbio.3002720.ref040","doi-asserted-by":"crossref","first-page":"e2118646119","DOI":"10.1073\/pnas.2118646119","article-title":"Ferroptosis regulation by the NGLY1\/NFE2L1 pathway","volume":"119","author":"GC Forcina","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"48","key":"pbio.3002720.ref041","doi-asserted-by":"crossref","first-page":"48021","DOI":"10.1074\/jbc.M308439200","article-title":"Deficiency of the Nrf1 and Nrf2 transcription factors results in early embryonic lethality and severe oxidative stress","volume":"278","author":"L Leung","year":"2003","journal-title":"J Biol Chem"},{"issue":"Pt B","key":"pbio.3002720.ref042","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.freeradbiomed.2015.06.008","article-title":"SKN-1\/Nrf, stress responses, and aging in Caenorhabditis elegans","volume":"88","author":"TK Blackwell","year":"2015","journal-title":"Free Radic Biol Med"},{"issue":"8","key":"pbio.3002720.ref043","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1001048","article-title":"RNAi screening implicates a SKN-1-dependent transcriptional response in stress resistance and longevity deriving from translation inhibition.","volume":"6","author":"J Wang","year":"2010","journal-title":"PLoS Genet."},{"issue":"5","key":"pbio.3002720.ref044","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.cmet.2012.04.007","article-title":"TOR signaling and rapamycin influence longevity by regulating SKN-1\/Nrf and DAF-16\/FoxO","volume":"15","author":"S Robida-Stubbs","year":"2012","journal-title":"Cell Metab"},{"issue":"5949","key":"pbio.3002720.ref045","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1126\/science.1177221","article-title":"Ribosomal protein S6 kinase 1 signaling regulates mammalian life span","volume":"326","author":"C Selman","year":"2009","journal-title":"Science"},{"issue":"6","key":"pbio.3002720.ref046","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.cmet.2007.05.006","article-title":"S6 kinase deletion suppresses muscle growth adaptations to nutrient availability by activating AMP kinase","volume":"5","author":"V Aguilar","year":"2007","journal-title":"Cell Metab"},{"issue":"1","key":"pbio.3002720.ref047","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.cmet.2012.05.010","article-title":"p70S6 kinase phosphorylates AMPK on serine 491 to mediate leptin\u2019s effect on food intake","volume":"16","author":"Y Dagon","year":"2012","journal-title":"Cell Metab"},{"issue":"12","key":"pbio.3002720.ref048","doi-asserted-by":"crossref","first-page":"e1009258","DOI":"10.1371\/journal.pgen.1009258","article-title":"A conserved role for AMP-activated protein kinase in NGLY1 deficiency.","volume":"16","author":"SY Han","year":"2020","journal-title":"PLoS Genet."},{"issue":"7334","key":"pbio.3002720.ref049","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/nature09706","article-title":"Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB","volume":"470","author":"W Mair","year":"2011","journal-title":"Nature"},{"issue":"29","key":"pbio.3002720.ref050","doi-asserted-by":"crossref","first-page":"17442","DOI":"10.1074\/jbc.270.29.17442","article-title":"A proteolytic pathway that recognizes ubiquitin as a degradation signal","volume":"270","author":"ES Johnson","year":"1995","journal-title":"J Biol Chem"},{"key":"pbio.3002720.ref051","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/978-1-61779-474-2_38","article-title":"Analysis of ubiquitin-dependent proteolysis in Caenorhabditis elegans","volume":"832","author":"A Segref","year":"2012","journal-title":"Methods Mol Biol"},{"issue":"5\u20136","key":"pbio.3002720.ref052","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s11357-016-9936-8","article-title":"Age-associated vulval integrity is an important marker of nematode healthspan.","volume":"38","author":"SF Leiser","year":"2016","journal-title":"Age (Dordr)."},{"issue":"9","key":"pbio.3002720.ref053","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.1534\/g3.118.200449","article-title":"Physiological Starvation Promotes Caenorhabditis elegans Vulval Induction.","volume":"8","author":"S Grimbert","year":"2018","journal-title":"G3 (Bethesda)."},{"issue":"3","key":"pbio.3002720.ref054","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1534\/genetics.118.301533","article-title":"The mTOR Target S6 Kinase Arrests Development in Caenorhabditis elegans When the Heat-Shock Transcription Factor Is Impaired","volume":"210","author":"P Chisnell","year":"2018","journal-title":"Genetics"},{"issue":"1","key":"pbio.3002720.ref055","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s10522-020-09906-7","article-title":"Inhibition of mTOR decreases insoluble proteins burden by reducing translation in C. elegans","volume":"22","author":"Z Yee","year":"2021","journal-title":"Biogerontology"},{"issue":"3","key":"pbio.3002720.ref056","doi-asserted-by":"crossref","first-page":"e1006695","DOI":"10.1371\/journal.pgen.1006695","article-title":"Transaldolase inhibition impairs mitochondrial respiration and induces a starvation-like longevity response in Caenorhabditis elegans.","volume":"13","author":"CF Bennett","year":"2017","journal-title":"PLoS Genet."},{"issue":"10","key":"pbio.3002720.ref057","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.exger.2006.06.059","article-title":"C. elegans models of age-associated neurodegenerative diseases: lessons from transgenic worm models of Alzheimer\u2019s disease","volume":"41","author":"CD Link","year":"2006","journal-title":"Exp Gerontol"},{"issue":"4","key":"pbio.3002720.ref058","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1080\/09687680410001712550","article-title":"Functional redundancy of two nucleoside transporters of the ENT family (CeENT1, CeENT2) required for development of Caenorhabditis elegans.","volume":"21","author":"PJ Appleford","year":"2004","journal-title":"Mol Membr Biol"},{"issue":"5","key":"pbio.3002720.ref059","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s00424-003-1103-2","article-title":"The equilibrative nucleoside transporter family, SLC29","volume":"447","author":"SA Baldwin","year":"2004","journal-title":"Pflugers Arch"},{"issue":"2","key":"pbio.3002720.ref060","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1534\/genetics.116.196774","article-title":"Alternative Polyadenylation Directs Tissue-Specific miRNA Targeting in Caenorhabditis elegans Somatic Tissues","volume":"206","author":"SM Blazie","year":"2017","journal-title":"Genetics"},{"issue":"6459","key":"pbio.3002720.ref061","doi-asserted-by":"crossref","DOI":"10.1126\/science.aax1971","article-title":"A lineage-resolved molecular atlas of C. elegans embryogenesis at single-cell resolution","volume":"365","author":"JS Packer","year":"2019","journal-title":"Science"},{"issue":"2","key":"pbio.3002720.ref062","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1101\/gr.114595.110","article-title":"A spatial and temporal map of C. elegans gene expression","volume":"21","author":"WC Spencer","year":"2011","journal-title":"Genome Res"},{"issue":"2","key":"pbio.3002720.ref063","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.ydbio.2004.12.012","article-title":"Transcriptional control and patterning of the pho-1 gene, an essential acid phosphatase expressed in the C. elegans intestine","volume":"279","author":"T Fukushige","year":"2005","journal-title":"Dev Biol"},{"issue":"35","key":"pbio.3002720.ref064","doi-asserted-by":"crossref","first-page":"36739","DOI":"10.1074\/jbc.M403415200","article-title":"Deletion of the intestinal peptide transporter affects insulin and TOR signaling in Caenorhabditis elegans","volume":"279","author":"B Meissner","year":"2004","journal-title":"J Biol Chem"},{"issue":"45","key":"pbio.3002720.ref065","doi-asserted-by":"crossref","first-page":"44657","DOI":"10.1074\/jbc.M307351200","article-title":"A reduction in intestinal cell pHi due to loss of the Caenorhabditis elegans Na+\/H+ exchanger NHX-2 increases life span","volume":"278","author":"K. Nehrke","year":"2003","journal-title":"J Biol Chem"},{"issue":"8","key":"pbio.3002720.ref066","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1038\/s42255-023-00863-2","article-title":"The pentose phosphate pathway in health and disease.","volume":"5","author":"T TeSlaa","year":"2023","journal-title":"Nat Metab"},{"issue":"3","key":"pbio.3002720.ref067","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1101\/gad.275107.115","article-title":"Nucleotide levels regulate germline proliferation through modulating GLP-1\/Notch signaling in C. elegans","volume":"30","author":"C Chi","year":"2016","journal-title":"Genes Dev"},{"issue":"3","key":"pbio.3002720.ref068","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1046\/j.1365-2958.1996.5341056.x","article-title":"A flexible partnership: the CytR anti-activator and the cAMP-CRP activator protein, comrades in transcription control","volume":"20","author":"P Valentin-Hansen","year":"1996","journal-title":"Mol Microbiol"},{"issue":"7","key":"pbio.3002720.ref069","doi-asserted-by":"crossref","DOI":"10.3390\/cells11071155","article-title":"NGLY1 Deficiency, a Congenital Disorder of Deglycosylation: From Disease Gene Function to Pathophysiology.","volume":"11","author":"A Pandey","year":"2022","journal-title":"Cells"},{"issue":"11","key":"pbio.3002720.ref070","article-title":"Drug screens of NGLY1 deficiency in worm and fly models reveal catecholamine, NRF2 and anti-inflammatory-pathway activation as potential clinical approaches.","volume":"12","author":"S Iyer","year":"2019","journal-title":"Dis Model Mech."},{"key":"pbio.3002720.ref071","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.57831","article-title":"A Drosophila screen identifies NKCC1 as a modifier of NGLY1 deficiency.","volume":"9","author":"DM Talsness","year":"2020","journal-title":"Elife"},{"issue":"1","key":"pbio.3002720.ref072","doi-asserted-by":"crossref","first-page":"5667","DOI":"10.1038\/s41467-023-40910-w","article-title":"Gut barrier defects, intestinal immune hyperactivation and enhanced lipid catabolism drive lethality in NGLY1-deficient Drosophila.","volume":"14","author":"A Pandey","year":"2023","journal-title":"Nat Commun."},{"issue":"3","key":"pbio.3002720.ref073","doi-asserted-by":"crossref","first-page":"165588","DOI":"10.1016\/j.bbadis.2019.165588","article-title":"Liver-specific deletion of Ngly1 causes abnormal nuclear morphology and lipid metabolism under food stress","volume":"1866","author":"H Fujihira","year":"2020","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"pbio.3002720.ref074","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/j.1474-9726.2006.00266.x","article-title":"Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans","volume":"6","author":"KZ Pan","year":"2007","journal-title":"Aging Cell"},{"issue":"6","key":"pbio.3002720.ref075","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR Signaling in Growth, Metabolism, and Disease.","volume":"168","author":"RA Saxton","year":"2017","journal-title":"Cell"},{"issue":"3","key":"pbio.3002720.ref076","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s42255-019-0038-7","article-title":"Molecular logic of mTORC1 signalling as a metabolic rheostat.","volume":"1","author":"AJ Valvezan","year":"2019","journal-title":"Nat Metab"},{"key":"pbio.3002720.ref077","doi-asserted-by":"crossref","first-page":"e08153","DOI":"10.7554\/eLife.08153","article-title":"Paradoxical resistance of multiple myeloma to proteasome inhibitors by decreased levels of 19S proteasomal subunits.","volume":"4","author":"D Acosta-Alvear","year":"2015","journal-title":"Elife"},{"issue":"13","key":"pbio.3002720.ref078","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1016\/j.celrep.2017.05.043","article-title":"Purine Nucleotide Availability Regulates mTORC1 Activity through the Rheb GTPase","volume":"19","author":"N Emmanuel","year":"2017","journal-title":"Cell Rep"},{"issue":"5","key":"pbio.3002720.ref079","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1016\/j.celrep.2017.10.029","article-title":"The mTORC1 Signaling Network Senses Changes in Cellular Purine Nucleotide Levels","volume":"21","author":"G Hoxhaj","year":"2017","journal-title":"Cell Rep"},{"issue":"6125","key":"pbio.3002720.ref080","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1126\/science.1228792","article-title":"Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1","volume":"339","author":"I Ben-Sahra","year":"2013","journal-title":"Science"},{"issue":"6274","key":"pbio.3002720.ref081","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1126\/science.aad0489","article-title":"mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle","volume":"351","author":"I Ben-Sahra","year":"2016","journal-title":"Science"},{"issue":"13","key":"pbio.3002720.ref082","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1080\/15384101.2015.1044188","article-title":"mTORC1 signaling activates NRF1 to increase cellular proteasome levels","volume":"14","author":"Y Zhang","year":"2015","journal-title":"Cell Cycle"},{"issue":"11","key":"pbio.3002720.ref083","doi-asserted-by":"crossref","first-page":"4120","DOI":"10.1073\/pnas.0500660102","article-title":"Liver-specific inactivation of the Nrf1 gene in adult mouse leads to nonalcoholic steatohepatitis and hepatic neoplasia","volume":"102","author":"Z Xu","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"pbio.3002720.ref084","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/j.cell.2017.10.003","article-title":"NRF1 Is an ER Membrane Sensor that Is Central to Cholesterol Homeostasis","volume":"171","author":"SB Widenmaier","year":"2017","journal-title":"Cell"},{"issue":"4","key":"pbio.3002720.ref085","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S1046-2023(03)00050-1","article-title":"Genome-wide RNAi screening in Caenorhabditis elegans.","volume":"30","author":"RS Kamath","year":"2003","journal-title":"Methods"},{"issue":"11","key":"pbio.3002720.ref086","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1534\/g3.112.003830","article-title":"large-scale screening for targeted knockouts in the Caenorhabditis elegans genome.","volume":"2","author":"Consortium CeDM","year":"2012","journal-title":"G3 (Bethesda)."},{"issue":"4","key":"pbio.3002720.ref087","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1534\/genetics.112.144204","article-title":"CloudMap: a cloud-based pipeline for analysis of mutant genome sequences","volume":"192","author":"G Minevich","year":"2012","journal-title":"Genetics"},{"issue":"1","key":"pbio.3002720.ref088","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1534\/genetics.115.179382","article-title":"High Efficiency, Homology-Directed Genome Editing in Caenorhabditis elegans Using CRISPR-Cas9 Ribonucleoprotein Complexes.","volume":"201","author":"A Paix","year":"2015","journal-title":"Genetics"},{"issue":"3","key":"pbio.3002720.ref089","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1534\/genetics.120.303564","article-title":"Melting dsDNA Donor Molecules Greatly Improves Precision Genome Editing in Caenorhabditis elegans","volume":"216","author":"KS Ghanta","year":"2020","journal-title":"Genetics"},{"issue":"5","key":"pbio.3002720.ref090","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/nmeth.2889","article-title":"Random and targeted transgene insertion in Caenorhabditis elegans using a modified Mos1 transposon.","volume":"11","author":"C Frokjaer-Jensen","year":"2014","journal-title":"Nat Methods."},{"issue":"7","key":"pbio.3002720.ref091","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis.","volume":"9","author":"J Schindelin","year":"2012","journal-title":"Nat Methods."},{"issue":"6","key":"pbio.3002720.ref092","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1093\/bioinformatics\/btt607","article-title":"Protter: interactive protein feature visualization and integration with experimental proteomic data","volume":"30","author":"U Omasits","year":"2014","journal-title":"Bioinformatics"}],"updated-by":[{"DOI":"10.1371\/journal.pbio.3002720","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T00:00:00Z","timestamp":1721692800000}}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3002720","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T19:09:40Z","timestamp":1721761780000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3002720"}},"subtitle":[],"editor":[{"given":"Ursula H.","family":"Jakob","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,7,11]]},"references-count":92,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3002720","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pbio.3002720","asserted-by":"object"}]},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,11]]}}}