{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:25:40Z","timestamp":1792686340459,"version":"4.5.0"},"reference-count":21,"publisher":"American Society of Hematology","issue":"16","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Intestinal iron absorption is activated during increased systemic demand for iron. The best-studied example is iron deficiency anemia, which increases intestinal iron absorption. Interestingly, the intestinal response to anemia is very similar to that of iron overload disorders, as both the conditions activate a transcriptional program that leads to a hyperabsorption of iron via the transcription factor hypoxia-inducible factor 2\u03b1 (HIF2\u03b1). However, pathways for selective targeting of intestine-mediated iron overload remain unknown. Nuclear receptor coactivator 4 (NCOA4) is a critical cargo receptor for autophagic breakdown of ferritin and the subsequent release of iron, in a process termed ferritinophagy. Our work demonstrates that NCOA4-mediated intestinal ferritinophagy is integrated into systemic iron demand via HIF2\u03b1. To demonstrate the importance of the intestinal HIF2\u03b1\/ferritinophagy axis in systemic iron homeostasis, whole-body and intestine-specific NCOA4\u2212\/\u2212 mouse lines were generated and assessed. The analyses revealed that the intestinal and systemic response to iron deficiency was not altered after disruption of intestinal NCOA4. However, in a mouse model of hemochromatosis, ablation of intestinal NCOA4 was protective against iron overload. Therefore, NCOA4 can be selectively targeted for the management of iron overload disorders without disrupting the physiological processes involved in the response to systemic iron deficiency.<\/jats:p>","DOI":"10.1182\/blood.2021013452","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T20:20:40Z","timestamp":1641500440000},"page":"2547-2552","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":48,"title":["Modulation of the HIF2\u03b1-NCOA4 axis in enterocytes attenuates iron loading in a mouse model of hemochromatosis"],"prefix":"10.1182","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-1134","authenticated-orcid":false,"given":"Nupur K.","family":"Das","sequence":"first","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, 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