{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:14:43Z","timestamp":1791983683338,"version":"4.4.0"},"reference-count":54,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T00:00:00Z","timestamp":1557705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["A17 278001972 - TRR 186"],"award-info":[{"award-number":["A17 278001972 - TRR 186"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK 1772"],"award-info":[{"award-number":["GRK 1772"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Integrative Research Institute for the Life Sciences","award":["Humboldt Universit\u00e4t zu Berlin"],"award-info":[{"award-number":["Humboldt Universit\u00e4t zu Berlin"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The circadian clock is an endogenous oscillator that controls daily rhythms in metabolism, physiology, and behavior. Although the timekeeping components differ among species, a common design principle is a transcription-translation negative feedback loop. However, it is becoming clear that other mechanisms can contribute to the generation of 24 h rhythms. Peroxiredoxins (Prxs) exhibit 24 h rhythms in their redox state in all kingdoms of life. In mammalian adrenal gland, heart and brown adipose tissue, such rhythms are generated as a result of an inactivating hyperoxidation reaction that is reduced by coordinated import of sulfiredoxin (Srx) into the mitochondria. However, a quantitative description of the Prx\/Srx oscillating system is still missing. We investigate the basic principles that generate mitochondrial Prx\/Srx rhythms using computational modeling. We observe that the previously described delay in mitochondrial Srx import, in combination with an appropriate separation of fast and slow reactions, is sufficient to generate robust self-sustained relaxation-like oscillations. We find that our conceptual model can be regarded as a series of three consecutive phases and two temporal switches, highlighting the importance of delayed negative feedback and switches in the generation of oscillations.<\/jats:p>","DOI":"10.3390\/ijms20092368","type":"journal-article","created":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T11:00:57Z","timestamp":1557745257000},"page":"2368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A Robust Model for Circadian Redox Oscillations"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6530-4628","authenticated-orcid":false,"given":"Marta","family":"del Olmo","sequence":"first","affiliation":[{"name":"Institute for Theoretical Biology, Charit\u00e9 and Humboldt-Universit\u00e4t zu Berlin, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Kramer","sequence":"additional","affiliation":[{"name":"Laboratory of Chronobiology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0414-7889","authenticated-orcid":false,"given":"Hanspeter","family":"Herzel","sequence":"additional","affiliation":[{"name":"Institute for Theoretical Biology, Charit\u00e9 and Humboldt-Universit\u00e4t zu Berlin, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1146\/annurev.genom.5.061903.175925","article-title":"Mammalian circadian biology: Elucidating genome-wide levels of temporal organization","volume":"5","author":"Lowrey","year":"2004","journal-title":"Annu. 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