ArticleHaematologica2015
The heme exporter Flvcr1 regulates expansion and differentiation of committed erythroid progenitors by controlling intracellular heme accumulation.
Article in Haematologica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 64 citations in OpenAlex.
- More than a ring: the emerging role of heme in angiogenesis.Cell communication and signaling : CCS · 2026Review
- Mitochondrial energetic failure underlies FLVCR1-related sensory neuropathy.Communications biology · 2026Article
- Iron: Regulation, redox homeostasis, and ferroptosis in cancer.Ferroptosis and oxidative stress · 2026Article
- FLVCR1-related diseases: from clinical heterogeneity to mechanistic insights.Brain communications · 2026Review
- Mechanisms of heme transport in the mitochondria.Biochemical Society transactions · 2025Review
- Outline of Iron Metabolism, with Emphasis on Erythroid Cells.Mediterranean journal of hematology and infectious diseases · 2025Review
- Update on heme biosynthesis, tissue-specific regulation, heme transport, relation to iron metabolism and cellular energy.Liver international : official journal of the International Association for the Study of the Liver · 2024Review
- Endogenous small molecule effectors in GATA transcription factor mechanisms governing biological and pathological processes.Experimental hematology · 2024Review
- Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus.Cell reports. Medicine · 2024Article
- Spatiotemporal expression and control of haemoglobin in space.Nature communications · 2024Article
- Unearthing FLVCR1a: tracing the path to a vital cellular transporter.Cellular and molecular life sciences : CMLS · 2024Review
- Biallelic variation in the choline and ethanolamine transportermedRxiv : the preprint server for health sciences · 2024Article
- FLVCR1a Controls Cellular Cholesterol Levels through the Regulation of Heme Biosynthesis and Tricarboxylic Acid Cycle Flux in Endothelial Cells.Biomolecules · 2024Article
- Mfsd7b facilitates choline transport and missense mutations affect choline transport function.Cellular and molecular life sciences : CMLS · 2023Article
- Endothelial cells require functional FLVCR1a during developmental and adult angiogenesis.Angiogenesis · 2023Article
- Integrative genetic analysis identifies FLVCR1 as a plasma-membrane choline transporter in mammals.Cell metabolism · 2023Article
- Are Antisense Long Non-Coding RNA Related to COVID-19?Biomedicines · 2022Article
- GAPDH is involved in the heme-maturation of myoglobin and hemoglobin.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Endothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor Microenvironment.Biomedicines · 2021Article
- Using the Zebrafish as a Genetic Model to Study Erythropoiesis.International journal of molecular sciences · 2021Review
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.