{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:14:28Z","timestamp":1788509668055,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/PR39040\/BRB\/10\/1882\/2020"],"award-info":[{"award-number":["BT\/PR39040\/BRB\/10\/1882\/2020"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["ICMR JRF\u20102018(021)"],"award-info":[{"award-number":["ICMR JRF\u20102018(021)"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>5\u2010oxoproline (5\u2010OP) or pyroglutamic acid is an intermediate in the degradation arc of the glutathione cycle. It is metabolized into glutamate through the action of the 5\u2010oxoprolinase enzyme, the only enzyme known to act on this metabolite. 5\u2010OP has long been known to be relatively inert with a proposed role as an osomoprotectant. Recent studies on the 5\u2010oxoprolinase enzyme in mammalian cells have, however, shown that knockdown or deletion of 5\u2010oxoprolinase makes mice (and humans) prone to heart failure, an effect ascribed to oxidative stress caused by a twofold increase in 5\u2010OP. To examine the consequences of 5\u2010oxoproline accumulation more rigorously, we created a yeast model for 5\u2010oxoproline accumulation. Using this model, we observed retardation of growth only when intracellular levels of 5\u2010OP were increased 12\u2010 to 20\u2010fold over normal levels. Performing an analysis of transcriptomic changes under these conditions, we observed a large number of genes were differentially regulated and while there was no unifying dysregulated pathway, there was an upregulation of various efflux pumps. Ultimately, modulating the expression of these genes by knockout or overexpression highlighted that many of the upregulated genes were involved in the cellular response to 5\u2010OP accumulation. However, our results failed to show any significant oxidative stress response. In conclusion, our study suggests a need to reevaluate previous suppositions of the 5\u2010OP induced oxidative stress response and proposes alternate mechanisms for this effect.<\/jats:p>","DOI":"10.1002\/2211-5463.70254","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T20:28:55Z","timestamp":1784147335000},"page":"1752-1765","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A yeast model of 5\u2010oxoproline accumulation reveals a general toleration to 5\u2010oxoproline"],"prefix":"10.1002","volume":"16","author":[{"given":"Pratiksha","family":"Dubey","sequence":"first","affiliation":[{"name":"Indian Institute of Science Education and Research Mohali  Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1139-4287","authenticated-orcid":false,"given":"Vaishnavi","family":"Sanjayan","sequence":"additional","affiliation":[{"name":"Indian Institute of Science Education and Research Mohali  Punjab India"},{"name":"Saint Louis University School of Medicine  St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7889-7688","authenticated-orcid":false,"given":"Praveen","family":"Singh","sequence":"additional","affiliation":[{"name":"CSIR\u2010Institute of Genomics &amp; Integrative Biology (IGIB)  Delhi India"},{"name":"Buck Institute for Research on Aging  Novato CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shantanu","family":"Sengupta","sequence":"additional","affiliation":[{"name":"CSIR\u2010Institute of Genomics &amp; Integrative Biology (IGIB)  Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1529-3769","authenticated-orcid":false,"given":"Anand Kumar","family":"Bachhawat","sequence":"additional","affiliation":[{"name":"Indian Institute of Science Education and Research Mohali  Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"288","article-title":"Pyroglutamic acid: throwing light on a lightly studied metabolite","volume":"102","author":"Kumar A","year":"2012","journal-title":"Curr Sci"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1756"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00235695"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(04)00300-X"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4838(98)00248-9"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002030050786"},{"key":"e_1_2_10_8_1","first-page":"149","article-title":"The biology and osmoadaptation of haloalkaliphilic methanotrophs","volume":"71","author":"Trotsenko IA","year":"2002","journal-title":"Mikrobiologiia"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700994"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.17793"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.27.288"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.71.4.1026"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aam8574"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvy187"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/126.11.2813"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(02)50957-5"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz931"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12041-023-01455-5"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1040627"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2012.156"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.327411"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.581892"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsyr.2004.06.003"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.15.3896"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.19.8822"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)42155-7"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.30.18150"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0922-338X(91)90269-M"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1310439110"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-017-8567-z"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.04.083"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.23.16040"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2007.05.003"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M512812200"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.3.719"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2008.08.006"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.727479"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.2000.278.5.E868"}],"container-title":["FEBS Open Bio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.70254","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/2211-5463.70254","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.70254","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T07:37:45Z","timestamp":1788507465000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/2211-5463.70254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":37,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/2211-5463.70254"],"URL":"https:\/\/doi.org\/10.1002\/2211-5463.70254","archive":["Portico"],"relation":{},"ISSN":["2211-5463","2211-5463"],"issn-type":[{"value":"2211-5463","type":"print"},{"value":"2211-5463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]},"assertion":[{"value":"2026-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}