{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T23:54:07Z","timestamp":1779321247744,"version":"3.51.4"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>4-hydroxy-TEMPO is a water-soluble nitroxide radical with potent antioxidant and redox-modulating properties. Its small molecular weight and membrane permeability enable it to act as a superoxide dismutase mimetic, efficiently scavenging reactive oxygen species and mitigating oxidative damage. In this study, we investigated the physiological and transcriptomic effects of 4-hydroxy-TEMPO in Saccharomyces cerevisiae, using wild-type and mutant strains deficient in key redox and DNA repair pathways (sod1\u0394, sod2\u0394, yap1\u0394, rad52\u0394). RNA-Seq analysis revealed widespread transcriptional reprogramming. Treatment with 4-hydroxy-TEMPO impaired cell growth, induced accumulation of cells with 1C (G1 phase) DNA content, and modulated chronological aging in a strain-dependent manner. Notably, low concentrations delayed aging in wild-type, yap1\u0394, and rad52\u0394 strains, while accelerating it in sod1\u0394 mutants, consistent with a hormetic response. Unlike TEMPO, 4-hydroxy-TEMPO exhibited markedly reduced translational toxicity, preserved polysome structure at high doses, and triggered a non-canonical, redox-dependent transcriptional program characterized by induction of stress-response genes together with unexpected up-regulation of multiple ribosomal protein genes. This was accompanied by a biphasic, genotype-specific hormetic response and a measurable genoprotective effect. RT-qPCR confirmed key transcriptional changes, linking transcriptome remodeling to functional outcomes.<\/jats:p>","DOI":"10.3390\/molecules31020376","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T11:11:17Z","timestamp":1768993877000},"page":"376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nitroxide Hormesis in Yeast: 4-Hydroxy-TEMPO Modulates Aging, and Cell Cycle"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9962-6788","authenticated-orcid":false,"given":"Mateusz","family":"Mo\u0142o\u0144","sequence":"first","affiliation":[{"name":"Faculty of Biology, Natural Protection, and Sustainable Development, University of Rzeszow, al. Tadeusza Rejtana 16C, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrycja","family":"Kielar","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Rzesz\u00f3w, al. Tadeusza Rejtana 16C, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6595-7351","authenticated-orcid":false,"given":"Eliza","family":"Molestak","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Biological Sciences, Maria Curie-Sk\u0142odowska University, Akademicka 19, 20-033 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Mo\u0142o\u0144","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Rzesz\u00f3w, al. Tadeusza Rejtana 16C, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3203-3195","authenticated-orcid":false,"given":"Ewelina","family":"Kuna","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Natural Protection, and Sustainable Development, University of Rzeszow, al. Tadeusza Rejtana 16C, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marek","family":"Biesiadecki","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Rzesz\u00f3w, al. Tadeusza Rejtana 16C, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Przemys\u0142aw","family":"Grela","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Biological Sciences, Maria Curie-Sk\u0142odowska University, Akademicka 19, 20-033 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Gonz\u00e1lez-Ibarra","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Biological Sciences, Maria Curie-Sk\u0142odowska University, Akademicka 19, 20-033 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1129-3553","authenticated-orcid":false,"given":"Sabina","family":"Galiniak","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Rzesz\u00f3w, al. Tadeusza Rejtana 16C, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13395","DOI":"10.1007\/s10973-022-11701-0","article-title":"Characterization and thermal decomposition kinetic study of promising antioxidante nitroxides","volume":"147","author":"Porto","year":"2022","journal-title":"J. Therm. Anal. Calorim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1021\/tx015571z","article-title":"The Mechanism by which 4-hydroxy-2,2,6,6-tetramethylpiperidene-1-oxyl (tempol) diverts peroxynitrite decomposition from nitrating to nitrosating species","volume":"15","author":"Bonini","year":"2002","journal-title":"Chem. Res. 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