{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:17:25Z","timestamp":1777396645167,"version":"3.51.4"},"reference-count":36,"publisher":"American Society for Cell Biology (ASCB)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:p> The eukaryotic cytosolic proteome is vulnerable to changes in proteostatic and redox balance caused by temperature, pH, oxidants, and xenobiotics. Cysteine-containing proteins are especially at risk, as the thiol side chain is subject to oxidation, adduction, and chelation by thiol-reactive compounds. The thiol-chelating heavy metal cadmium is a highly toxic environmental pollutant demonstrated to induce the heat shock response and recruit protein chaperones to sites of presumed protein aggregation in the budding yeast Saccharomyces cerevisiae. However, endogenous targets of cadmium toxicity responsible for these outcomes are largely unknown. Using fluorescent protein fusion to cytosolic proteins with known redox-active cysteines, we identified the yeast glycolytic enzyme triose phosphate isomerase as being aggregation-prone in response to cadmium and to glucose depletion in chronologically aging cultures. Cadmium-induced aggregation was limited to newly synthesized Tpi1 that was recruited to foci containing the disaggregase Hsp104 and the peroxiredoxin chaperone Tsa1. Misfolding of nascent Tpi1 in response to both cadmium and glucose-depletion stress required both cysteines, implying that thiol status in this protein directly influences folding. We also demonstrate that cadmium proteotoxicity is conserved between yeast and human cells, as HEK293 and HCT116 cell lines exhibit recruitment of the protein chaperone Hsp70 to visible foci. Moreover, human TPI, mutations in which cause a glycolytic deficiency syndrome, also forms aggregates in response to cadmium treatment, suggesting that this conserved enzyme is folding-labile and may be a useful endogenous model for investigating thiol-specific proteotoxicity. <\/jats:p>","DOI":"10.1091\/mbc.e18-10-0616","type":"journal-article","created":{"date-parts":[[2019,1,2]],"date-time":"2019-01-02T12:18:57Z","timestamp":1546431537000},"page":"554-565","source":"Crossref","is-referenced-by-count":17,"title":["Thiol stress\u2013dependent aggregation of the glycolytic enzyme triose phosphate isomerase in yeast and human cells"],"prefix":"10.1091","volume":"30","author":[{"given":"Amy E.","family":"Ford","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Texas McGovern Medical School at Houston, Houston, TX 77030"},{"name":"MD Anderson UT Health Graduate School of Biomedical Sciences, Houston, TX 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Denicourt","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology, University of Texas McGovern Medical School at Houston, Houston, TX 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin A.","family":"Morano","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Texas McGovern Medical School at Houston, Houston, TX 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"13155","DOI":"10.1074\/jbc.M113.530014","volume":"289","author":"Abrams JL","year":"2014","journal-title":"J Biol Chem"},{"key":"B2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0268-960X(95)90022-5","volume":"9","author":"Arya R","year":"1995","journal-title":"Blood Rev"},{"key":"B3","doi-asserted-by":"crossref","first-page":"41893","DOI":"10.1074\/jbc.M111.296236","volume":"286","author":"Brandes N","year":"2011","journal-title":"J Biol Chem"},{"key":"B4","doi-asserted-by":"crossref","first-page":"e00306","DOI":"10.7554\/eLife.00306","volume":"2","author":"Brandes N","year":"2013","journal-title":"Elife"},{"key":"B5","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1083\/jcb.200807043","volume":"183","author":"Buchan JR","year":"2008","journal-title":"J Cell Biol"},{"key":"B6","doi-asserted-by":"crossref","first-page":"a004374","DOI":"10.1101\/cshperspect.a004374","volume":"3","author":"Chen B","year":"2011","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B7","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1002\/yea.715","volume":"18","author":"Compagno C","year":"2001","journal-title":"Yeast"},{"key":"B8","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1038\/ncb2838","volume":"15","author":"Escusa-Toret S","year":"2013","journal-title":"Nat Cell Biol"},{"key":"B9","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nature02046","volume":"425","author":"Ghaemmaghami S","year":"2003","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.cell.2016.05.006","volume":"166","author":"Hanz\u00e9n S","year":"2016","journal-title":"Cell"},{"key":"B11","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/cfg.449","volume":"6","author":"Howson R","year":"2005","journal-title":"Comp Funct Genomics"},{"key":"B13","doi-asserted-by":"crossref","first-page":"5073","DOI":"10.1242\/jcs.107029","volume":"125","author":"Jacobson T","year":"2012","journal-title":"J Cell Sci"},{"key":"B12","doi-asserted-by":"crossref","first-page":"e00490","DOI":"10.1128\/MCB.00490-16","volume":"37","author":"Jacobson T","year":"2017","journal-title":"Mol Cell Biol"},{"key":"B14","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.cell.2004.05.002","volume":"117","author":"Jang HH","year":"2004","journal-title":"Cell"},{"key":"B15","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/361369a0","volume":"361","author":"Jungmann J","year":"1993","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1038\/ncb863","volume":"4","author":"Kim S","year":"2002","journal-title":"Nat Cell Biol"},{"key":"B17","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1534\/genetics.166.2.729","volume":"166","author":"Kshirsagar M","year":"2004","journal-title":"Genetics"},{"key":"B18","doi-asserted-by":"crossref","first-page":"e67902","DOI":"10.1371\/journal.pone.0067902","volume":"8","author":"Lee S","year":"2013","journal-title":"PLoS One"},{"key":"B19","doi-asserted-by":"crossref","first-page":"10420","DOI":"10.1074\/jbc.M513346200","volume":"281","author":"Le Moan N","year":"2006","journal-title":"J Biol Chem"},{"key":"B21","doi-asserted-by":"crossref","first-page":"6609","DOI":"10.1021\/bi00480a009","volume":"29","author":"Lolis E","year":"1990","journal-title":"Biochemistry"},{"key":"B22","doi-asserted-by":"crossref","first-page":"778","DOI":"10.15252\/embj.201489524","volume":"34","author":"Miller SBM","year":"2015","journal-title":"EMBO J"},{"key":"B23","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1534\/genetics.111.128033","volume":"190","author":"Morano KA","year":"2012","journal-title":"Genetics"},{"key":"B24","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1038\/nprot.2006.236","volume":"1","author":"Nolan T","year":"2006","journal-title":"Nat Protoc"},{"key":"B25","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1042\/bst0300030","volume":"30","author":"Ol\u00e1h J","year":"2002","journal-title":"Biochem Soc Trans"},{"key":"B26","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.1371\/journal.pone.0000030","volume":"1","author":"Ralser M","year":"2006","journal-title":"PLoS One"},{"key":"B27","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/ncb3600","volume":"19","author":"Saad S","year":"2017","journal-title":"Nat Cell Biol"},{"key":"B28","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.bbrc.2008.05.052","volume":"372","author":"Sharma SK","year":"2008","journal-title":"Biochem Biophys Res Commun"},{"key":"B29","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3390\/biom4010252","volume":"4","author":"Tam\u00e1s MJ","year":"2014","journal-title":"Biomolecules"},{"key":"B30","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1089\/ars.2012.5033","volume":"18","author":"Toledano MB","year":"2013","journal-title":"Antioxid Redox Signal"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e07-10-1004"},{"key":"B32","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1016\/j.cell.2015.08.041","volume":"162","author":"Wallace EWJ","year":"2015","journal-title":"Cell"},{"key":"B33","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1126\/science.1209038","volume":"334","author":"Walter P","year":"2011","journal-title":"Science"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e12-06-0447"},{"key":"B35","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1242\/jcs.144022","volume":"127","author":"Weids AJ","year":"2014","journal-title":"J Cell Sci"},{"key":"B36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep24554","volume":"6","author":"Weids AJ","year":"2016","journal-title":"Sci Rep"},{"key":"B37","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1021\/tx300264x","volume":"25","author":"West JD","year":"2012","journal-title":"Chem Res Toxicol"}],"container-title":["Molecular Biology of the Cell"],"original-title":[],"language":"en","deposited":{"date-parts":[[2019,7,14]],"date-time":"2019-07-14T14:11:45Z","timestamp":1563113505000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.molbiolcell.org\/doi\/10.1091\/mbc.E18-10-0616"}},"subtitle":[],"editor":[{"given":"Thomas D.","family":"Fox","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1091\/mbc.E18-10-0616"],"URL":"https:\/\/doi.org\/10.1091\/mbc.e18-10-0616","relation":{},"ISSN":["1059-1524","1939-4586"],"issn-type":[{"value":"1059-1524","type":"print"},{"value":"1939-4586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3]]}}}