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

Haematologica
Sonia MercurioEmanuela Tolosano

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 regu...Continue Reading

Citations

Aug 4, 2015·European Journal of Haematology·M Tarek Elghetany
Jun 11, 2015·European Journal of Haematology·Sonia MercurioDeborah Chiabrando
Feb 2, 2018·Frontiers in Physiology·Shavonn R WhitenZach N Adelman
Aug 3, 2017·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Marco CastoriDeborah Chiabrando
Aug 5, 2018·Journal of Cellular Biochemistry·Ying ShenPeng Shang
Oct 17, 2019·Antioxidants·J Catharina DuvigneauAndrey V Kozlov
Oct 28, 2019·IUBMB Life·Te Ling, John D Crispino
Mar 8, 2020·Histochemistry and Cell Biology·Sanja Vignjević PetrinovićVladan Čokić
Mar 14, 2018·International Journal of Oncology·Changliang PengChunzheng Gao
Aug 11, 2017·Metallomics : Integrated Biometal Science·Martin D Kafina, Barry H Paw
Oct 26, 2018·Frontiers in Neuroscience·Deborah ChiabrandoEmanuela Tolosano
May 30, 2020·International Journal of Molecular Sciences·Deborah ChiabrandoEmanuela Tolosano
Apr 4, 2019·Frontiers in Oncology·Francesca DestefanisEmanuela Tolosano
May 28, 2020·Proceedings of the National Academy of Sciences of the United States of America·Peng HuangXiangmin Xu
Dec 13, 2017·Cell Death and Differentiation·Sara PetrilloEmanuela Tolosano
Feb 6, 2021·Neuroscience and Biobehavioral Reviews·Deborah ChiabrandoEmanuela Tolosano
Aug 10, 2018·Free Radical Biology & Medicine·Rebecca K DoneganAmit R Reddi
Oct 7, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Ian G ChambersAmit R Reddi

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