{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T03:21:42Z","timestamp":1789701702100,"version":"4.0.1"},"reference-count":121,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,7]],"date-time":"2023-05-07T00:00:00Z","timestamp":1683417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["HL153144"],"award-info":[{"award-number":["HL153144"]}]},{"name":"National Institutes of Health","award":["HL150927"],"award-info":[{"award-number":["HL150927"]}]},{"name":"National Institutes of Health","award":["HL153144"],"award-info":[{"award-number":["HL153144"]}]},{"name":"APC","award":["HL153144"],"award-info":[{"award-number":["HL153144"]}]},{"name":"APC","award":["HL150927"],"award-info":[{"award-number":["HL150927"]}]},{"name":"APC","award":["HL153144"],"award-info":[{"award-number":["HL153144"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Cytoprotective heme oxygenases derivatize heme to generate carbon monoxide, ferrous iron, and isomeric biliverdins, followed by rapid NAD(P)H-dependent biliverdin reduction to the antioxidant bilirubin. Recent studies have implicated biliverdin IX\u03b2 reductase (BLVRB) in a redox-regulated mechanism of hematopoietic lineage fate restricted to megakaryocyte and erythroid development, a function distinct and non-overlapping from the BLVRA (biliverdin IX\u03b1 reductase) homologue. In this review, we focus on recent progress in BLVRB biochemistry and genetics, highlighting human, murine, and cell-based studies that position BLVRB-regulated redox function (or ROS accumulation) as a developmentally tuned trigger that governs megakaryocyte\/erythroid lineage fate arising from hematopoietic stem cells. BLVRB crystallographic and thermodynamic studies have elucidated critical determinants of substrate utilization, redox coupling and cytoprotection, and have established that inhibitors and substrates bind within the single-Rossmann fold. These advances provide unique opportunities for the development of BLVRB-selective redox inhibitors as novel cellular targets that retain potential for therapeutic applicability in hematopoietic (and other) disorders.<\/jats:p>","DOI":"10.3390\/antiox12051058","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T01:32:53Z","timestamp":1683509573000},"page":"1058","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Metabolic Functions of Biliverdin IX\u03b2 Reductase in Redox-Regulated Hematopoietic Cell Fate"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6527-8503","authenticated-orcid":false,"given":"Wadie F.","family":"Bahou","sequence":"first","affiliation":[{"name":"Department of Medicine, School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Marchenko","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5549-0383","authenticated-orcid":false,"given":"Natasha M.","family":"Nesbitt","sequence":"additional","affiliation":[{"name":"Blood Cell Technologies, 25 Health Sciences Drive, Stony Brook, NY 11790, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3919","DOI":"10.1021\/cr400415k","article-title":"Heme enzyme structure and function","volume":"114","author":"Poulos","year":"2014","journal-title":"Chem. 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