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HIFs are heterodimers comprised of an O<jats:sub>2<\/jats:sub>-regulated HIF-1\u03b1 or HIF-2\u03b1 subunit and a constitutively expressed HIF-1\u03b2 subunit. Induction of HIF activity under conditions of reduced O<jats:sub>2<\/jats:sub>availability requires stabilization of HIF-1\u03b1 and HIF-2\u03b1 due to reduced prolyl hydroxylation, dimerization with HIF-1\u03b2, and interaction with coactivators due to decreased asparaginyl hydroxylation. Stimuli other than hypoxia, such as nitric oxide and reactive oxygen species, can also activate HIFs. HIF-1 and HIF-2 are essential for acute O<jats:sub>2<\/jats:sub>sensing by the carotid body, and their coordinated transcriptional activation is critical for physiological adaptations to chronic hypoxia including erythropoiesis, vascularization, metabolic reprogramming, and ventilatory acclimatization. In contrast, intermittent hypoxia, which occurs in association with sleep-disordered breathing, results in an imbalance between HIF-1\u03b1 and HIF-2\u03b1 that causes oxidative stress, leading to cardiorespiratory pathology.<\/jats:p>","DOI":"10.1152\/physrev.00030.2011","type":"journal-article","created":{"date-parts":[[2012,7,19]],"date-time":"2012-07-19T08:10:52Z","timestamp":1342685452000},"page":"967-1003","source":"Crossref","is-referenced-by-count":599,"title":["Adaptive and Maladaptive Cardiorespiratory Responses to Continuous and Intermittent Hypoxia Mediated by Hypoxia-Inducible Factors 1 and 2"],"prefix":"10.1152","volume":"92","author":[{"given":"Nanduri R.","family":"Prabhakar","sequence":"first","affiliation":[{"name":"Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, Biological Sciences Division, University of Chicago, Chicago, Illinois; and Vascular Program, Institute for Cell Engineering; Departments of Pediatrics, Medicine, Oncology, 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