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We show that antioxidant enzymes are neither homeostatically induced nor are peroxide levels increased in hypoxia. Additionally, forced expression of diverse antioxidant enzymes, all of which diminish peroxide, had disparate effects on HIF1\u03b1 protein stability. Moreover, decrease in lipid peroxides by glutathione peroxidase-4 or superoxide by mitochondrial SOD, failed to influence HIF1\u03b1 protein stability. These data show that mitochondrial, cytosolic or lipid ROS were not necessary for HIF1\u03b1 stability, and favor a model where mitochondria contribute to hypoxic adaptation as oxygen consumers.<\/jats:p>","DOI":"10.7554\/elife.72873","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T08:03:08Z","timestamp":1633075388000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.72873","source":"Crossref","is-referenced-by-count":29,"title":["HIF1\u03b1 stabilization in hypoxia is not oxidant-initiated"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5017-9887","authenticated-orcid":true,"given":"Amit","family":"Kumar","sequence":"first","affiliation":[{"name":"Burke Neurological Institute, White Plains","place":["New York, United States"]},{"name":"Brain and Mind Research Institute, Weill Medical College of Cornell University","place":["New York, United States"]},{"name":"Department of Neurology, Weill Medical College 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