NDLI: The heme exporter Flvcr1 regulates expansion and differentiation of committed erythroid progenitors by controlling intracellular heme accumulation

Content Provider	PubMed Central
Author	Mercurio, Sonia Petrillo, Sara Deborah, Chiabrando Bassi, Zuni Irma Gays, Dafne Camporeale, Annalisa Vacaru, Andrei Barbara, Miniscalco Giulio, Valperga Lorenzo, Silengo Fiorella, Altruda Baron, Margaret H. Santoro, Massimo Mattia Tolosano, Emanuela
Copyright Year	2015
Abstract	Feline leukemia virus subgroup C receptor 1 (Flvcr1) encodes two heme exporters: FLVCR1a, which localizes to the plasma membrane, and FLVCR1b, which localizes to mitochondria. Here, we investigated the role of the two Flvcr1 isoforms during erythropoiesis. We showed that, in mice and zebrafish, Flvcr1a is required for the expansion of committed erythroid progenitors but cannot drive their terminal differentiation, while Flvcr1b contributes to the expansion phase and is required for differentiation. FLVCR1a-down-regulated K562 cells have defective proliferation, enhanced differentiation, and heme loading in the cytosol, while FLVCR1a/1b-deficient K562 cells show impairment in both proliferation and differentiation, and accumulate heme in mitochondria. These data support a model in which the coordinated expression of Flvcr1a and Flvcr1b contributes to control the size of the cytosolic heme pool required to sustain metabolic activity during the expansion of erythroid progenitors and to allow hemoglobinization during their terminal maturation. Consistently, reduction or increase of the cytosolic heme rescued the erythroid defects in zebrafish deficient in Flvcr1a or Flvcr1b, respectively. Thus, heme export represents a tightly regulated process that controls erythropoiesis.
Related Links	http://dx.doi.org/10.3324/haematol.2014.114488
Ending Page	729
Page Count	10
Starting Page	720
File Format	PDF
ISSN	03906078
e-ISSN	15928721
Journal	Haematologica
Issue Number	6
Volume Number	100
Language	English
Publisher	Ferrata Storti Foundation
Publisher Date	2015-06-01
Access Restriction	Open
Rights Holder	Ferrata Storti Foundation
Subject Keyword	Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Hematology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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