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During hibernation, the 13\u2010lined ground squirrel (<jats:italic>Ictidomys tridecemlineatus<\/jats:italic>) undergoes a global suppression of energetically expensive processes such as transcription and translation, while selectively upregulating certain genes\/proteins to mitigate torpor\u2010related damage. Antioxidant defenses are critical for preventing damage caused by reactive oxygen species (ROS) during torpor and arousal, and Nrf2 is a critical regulator of these antioxidant genes. This study analysed the relative protein expression levels of Nrf2, KEAP1, small Mafs (MafF, MafK and MafG) and catalase and the regulation of Nrf2 transcription factors by post\u2010translational modifications (PTMs) and protein\u2010protein interactions with a negative regulator (KEAP1) during hibernation. It was found that a significant increase in MafK during late torpor predicated an increase in relative Nrf2 and catalase levels seen in arousal. Additionally, Nrf2\u2010KEAP1 protein\u2010protein interactions and Nrf2 PTMs, including serine phosphorylation and lysine acetylation, were responsive to cycles of torpor\u2010arousal with peak responses occurring during arousal. These peaks seen during arousal correspond to a surge in oxygen consumption, which causes increased ROS production. Thus, these regulatory mechanisms could be important during hibernation because they provide mechanisms for mitigating the deleterious effects of oxidative stress by modifying Nrf2 expression and function in an energetically inexpensive manner.<\/jats:p>","DOI":"10.1002\/cbf.3627","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T06:25:30Z","timestamp":1614147930000},"page":"623-635","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Modulating Nrf2 transcription factor activity: Revealing the regulatory mechanisms of antioxidant defenses during hibernation in 13\u2010lined ground squirrels"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2373-232X","authenticated-orcid":false,"given":"Shannon N.","family":"Tessier","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Department of Biology Carleton University  Ottawa Ontario 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