Abcb10 physically interacts with mitoferrin-1 (Slc25a37) to enhance its stability and function in the erythroid mitochondria

Chen, Wen; Paradkar, Prasad N.; Li, Liangtao; Pierce, Eric T.; Langer, Nathaniel B.; Takahashi-Makise, Naoko; Hyde, Brigham B.; Shirihai, Orian S.; Ward, Diane McVey; Kaplan, Jerry; Paw, Barry H.

doi:10.1073/pnas.0904519106

Cited by 196 publications

(196 citation statements)

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“…6 Porin (Calbiochem, San Diego, CA, USA) and a-actin (Novus Biologicals, Littleton, CO, USA) antibodies were used according to manufacturer's instruction. Mfrn1 and BCL-xL (Cell Signalling, Danvers, MA, USA) antibodies were used as previously described 10,23,24 (Supplementary Figure S1).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, ABC-me (ABCB10) has been demonstrated to be required for maximal (not basal) iron import into mitochondria during in vitro erythroid differentiation, as it stabilizes the iron importer mitoferrin 1 (Mfrn1). 10 The mitochondrial topology of ABC-me transporter makes it a likely candidate as a novel exporter having a role in mitochondria detoxification and/or regulating the compartmentalization of heme biosynthesis intermediates between mitochondria and cytosol. Finely tuned compartmentalization and proper mitochondrial function are not only relevant for the rates of heme production but also are essential for cell viability, as accumulation of heme intermediates or regulators of their production in cytosol and/or mitochondria can lead to oxidative stress and toxicity.…”

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confidence: 99%

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The mitochondrial transporter ABC-me (ABCB10), a downstream target of GATA-1, is essential for erythropoiesis in vivo

et al. 2012

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The mitochondrial transporter ATP binding cassette mitochondrial erythroid (ABC-me/ABCB10) is highly induced during erythroid differentiation by GATA-1 and its overexpression increases hemoglobin production rates in vitro. However, the role of ABC-me in erythropoiesis in vivo is unknown. Here we report for the first time that erythrocyte development in mice requires ABC-me. ABC-meÀ/À mice die at day 12.5 of gestation, showing nearly complete eradication of primitive erythropoiesis and lack of hemoglobinized cells at day 10.5. ABC-meÀ/À erythroid cells fail to differentiate because they exhibit a marked increase in apoptosis, both in vivo and ex vivo. Erythroid precursors are particularly sensitive to oxidative stress and ABC-me in the heart and its yeast ortholog multidrug resistance-like 1 have been shown to protect against oxidative stress. Thus, we hypothesized that increased apoptosis in ABC-meÀ/À erythroid precursors was caused by oxidative stress. Within this context, ABC-me deletion causes an increase in mitochondrial superoxide production and protein carbonylation in erythroid precursors. Furthermore, treatment of ABC-meÀ/À erythroid progenitors with the mitochondrial antioxidant MnTBAP (superoxide dismutase 2 mimetic) supports survival, ex vivo differentiation and increased hemoglobin production. Altogether, our findings demonstrate that ABC-me is essential for erythropoiesis in vivo. Cell Death and Differentiation (2012) 19, 1117-1126 doi:10.1038/cdd.2011; published online 13 January 2012A central event during erythroid development is the induction of the components responsible for heme biosynthesis. Although heme is also produced in non-erythroid cells, its biosynthesis is specifically regulated during erythroid differentiation. 1-3 Thus, mutations in some specific genes involved in heme production have been shown to cause several human blood disorders, such as sideroblastic anemias. 4 This type of anemia is characterized by abnormal erythroid differentiation with a reduction in the total number of erythrocytes. 4 In addition, there are idiopathic anemias (either genetic or druginduced) in which the primary molecular defect is unknown. Recently, a novel bioinformatic approach identified new genes involved in heme biosynthesis that could be potential therapeutic targets for these disorders. 5 Furthermore, this large-scale computational screen identified again the ATP Binding Cassette mitochondrial erythroid transporter (ABCme/ABCB10) as an important protein for heme biosynthesis. 5 We previously identified ABC-me as a downstream target of an essential transcription factor for terminal erythroid differentiation, namely GATA-1. 6 ABC-me is a homodimeric transporter located in the inner mitochondrial membrane, which shows the highest expression levels in erythroid tissues. 6,7 Importantly, during early stages of mouse development (day 10 post coitus, pc), ABC-me expression is detected exclusively at the primitive sites of hematopoiesis, namely the yolk sac blood islands. 6 Furthermore, at day 9.5-10.5 pc,...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

The mitochondrial transporter ABC-me (ABCB10), a downstream target of GATA-1, is essential for erythropoiesis in vivo

et al. 2012

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“…SLC25A37 (Mitoferrin-1; Mfrn1), a member of the solute carrier family localized in the mitochondrial inner membrane, functions as an essential iron importer for the synthesis of mitochondrial heme and iron-sulfur clusters in erythroblasts. [25] There have been no studies about genetic polymorphisms of SLC25A37 to date. In this study, minor allele homozygotes (G) of rs7830129 of SLC25A37 might be associated (P = 4.141x10 -4 , in recessive model; Table 5) with increased absorption of simvastatin.…”

Section: Discussionmentioning

confidence: 99%

Screening study for genetic polymorphisms affecting pharmacokinetics of simvastatin

Kim

Lee

et al. 2016

Transl Clin Pharmacol

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Simvastatin reduces plasma cholesterol by inhibiting HMG-CoA reductase (HMGR) and is widely used in the treatment of hypercholesterolemia. To screening the possible genetic factors affecting the pharmacokinetics (PK) of simvastatin, 35 male Korean volunteers were enrolled from two separate bioequivalence studies. Each subject was administered 20 mg simvastatin and reference drug PK parameters were used. We used Illumina Human610Quad v1.0 DNA Analysis BeadChip for whole genome SNPs analysis and whole genome genotyping data was processed by linear regression analysis for PK parameters of drug metabolizing enzymes and transporters. We found 145 significant SNPs (P < 0.01) in C max , 135 significant SNPs (P < 0.01) in T max and 85 significant SNPs (P < 0.01) in AUC inf from whole genome analysis. In particular, we found that the ABCC2 gene had a significant effect on C max and AUC inf . These results could provide information of possible candidate genes for personalized simvastatin therapy.

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“…A study suggested that ABCB10 might mediate this translocating event [60]. However, other biochemical and genetic studies indicate that ABCB10 is more likely to be involved in the final step of heme synthesis, as discussed above [59,61].…”

Section: Transport Of Heme Synthesis Intermediatesmentioning

confidence: 98%

Regulation of heme biosynthesis and transport in metazoa

Sun

Cheng

Chen

2015

Sci. China Life Sci.

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Heme is an iron-containing tetrapyrrole that plays a critical role in regulating a variety of biological processes including oxygen and electron transport, gas sensing, signal transduction, biological clock, and microRNA processing. Most metazoan cells synthesize heme via a conserved pathway comprised of eight enzyme-catalyzed reactions. Heme can also be acquired from food or extracellular environment. Cellular heme homeostasis is maintained through the coordinated regulation of synthesis, transport, and degradation. This review presents the current knowledge of the synthesis and transport of heme in metazoans and highlights recent advances in the regulation of these pathways. heme, iron, synthesis, transport, regulation Citation:Sun FX, Cheng YJ, Chen CY. Regulation of heme biosynthesis and transport in metazoa.

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Abcb10 physically interacts with mitoferrin-1 (Slc25a37) to enhance its stability and function in the erythroid mitochondria

Cited by 196 publications

References 38 publications

The mitochondrial transporter ABC-me (ABCB10), a downstream target of GATA-1, is essential for erythropoiesis in vivo

The mitochondrial transporter ABC-me (ABCB10), a downstream target of GATA-1, is essential for erythropoiesis in vivo

Screening study for genetic polymorphisms affecting pharmacokinetics of simvastatin

Regulation of heme biosynthesis and transport in metazoa

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