Navigation Links
Nature study reveals loss of essential blood cell gene leads to anemia

Athens, Ga. Scientists at the University of Georgia, Harvard Medical School and the University of Utah have discovered a new gene that regulates heme synthesis in red blood cell formation. Heme is the deep-red, iron-containing component of hemoglobin, the protein in red blood cells responsible for transporting oxygen in the blood.

The study was published online Nov. 7 and will be in the Nov. 22 print edition of the journal Nature. The findings promise to advance the biomedical community's understanding and treatment of human anemias and mitochondrial diseases, both known and unknown.

The geneknown as mitochondrial ATPase inhibitory factor-1 gene or Atpif1was uncovered from a chemical mutagenesis screen of zebrafish, an organism which shares many of the same genes that regulate blood development in humans.

"With zebrafish, we are able to accelerate natural disease processes and screen for many more mutations in blood than we could ever see in random circumstance of human patients," said study senior co-author Dr. Barry Paw, a hematologist and associate professor of medicine at Harvard Medical School.

"In our case, we were looking for mutants that were bloodless, presumably because whatever gene that was inactivated by the random mutation must be critical for blood development, if one of these embryos were bloodless."

That is what Paw and his team found when they stumbled upon the particular "bloodless" mutant zebrafish called pinotage. The loss of the Atpif1 gene was the cause of the fish's severe anemia.

The next step for the team was to determine if the anemia was a defect of iron metabolism or heme homeostasis. Collaborating with molecular biologist Jerry Kaplan at the University of Utah, the researchers discovered a possible link between Atpif1 and ferrochelatase, the terminal enzyme in heme synthesis.

UGA microbiologist Harry Dailey, a leading authority in the structure and function of ferrochelatase, was brought on board. Collaborative work between the Paw and Dailey laboratories uncovered a broader mechanistic role for Atpif1 in regulating the enzymatic activity of ferrochelatase.

"We believe that the two iron-two sulfur (2Fe- 2S) cluster of ferrochelatase allows it to sense certain metabolic fluxes in the cell and respond to those fluxes in an appropriate way," said Dailey, who is a professor of microbiology and director of the UGA Biomedical and Health Sciences Institute. "When Atpf1 is deficient, there is a change in the mitochondrial pH/redox potential. This change is sensed by the cluster, and ferrochelatase activity is turned down, which results in diminished heme synthesis."

The researchers also were able to produce data on the human version of Atpif1, noting its functional importance for normal red blood cell differentiation as well as how a deficiency may contribute to human diseasessuch as congenital anemias and disorders related to dysfunctional mitochondria, the organelles that power the cell.

Overall, Dailey believes the study's results will impact the field of red blood cell development significantly with the establishment of the ferrochelatase [2Fe-2S] cluster as a new regulatory component in heme synthesis. New areas of investigation will open, he said, and the molecular basis of currently undefined red blood cell-based syndromes and diseases may be revealed.


Contact: Harry Dailey
University of Georgia

Related biology news :

1. 15-year study: When it comes to creating wetlands, Mother Nature is in charge
2. Epigenetic signatures direct the repair potential of reprogrammed cells
3. Nature: Video reveals wave character of particles
4. 2012 ACMG Foundation/Signature Genomic Laboratories Travel Award winner announced
5. Stoneflies mapped across Ohio, with implications for water quality and nature conservation
6. Gene signature helps identify risk of relapse in lung cancer patients
7. Natures billion-year-old battery key to storing energy
8. Can natures beauty lift citizens from poverty?
9. Biosignatures distinguish between tuberculosis and sarcoidosis
10. Nature: Microscope looks into cells of living fish
11. Nature or nurture? It may depend on where you live
Post Your Comments:
(Date:6/22/2016)...  The American College of Medical Genetics and Genomics was ... as one of the fastest-growing trade shows during the Fastest ... in Las Vegas . ... in each of the following categories: net square feet of ... attendees. The 2015 ACMG Annual Meeting was ranked 23 out ...
(Date:6/16/2016)... , June 16, 2016 ... size is expected to reach USD 1.83 billion ... Grand View Research, Inc. Technological proliferation and increasing ... applications are expected to drive the market growth. ... , The development of advanced multimodal ...
(Date:6/3/2016)... Das DOTM (Department ... hat ein 44 Millionen $-Projekt ... einschließlich Personalisierung, Registrierung und IT-Infrastruktur, an Decatur ... Implementierung von Identitätsmanagementlösungen. Zahlreiche renommierte internationale Anbieter ... aber Decatur wurde als konformste und innovativste ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... , ... June 27, 2016 , ... ... bring innovative medical technologies, services and solutions to the healthcare market. The company's ... of various distribution, manufacturing, sales and marketing strategies that are necessary to help ...
(Date:6/27/2016)... 27, 2016  Liquid Biotech USA ... of a Sponsored Research Agreement with The University ... (CTCs) from cancer patients.  The funding will be ... correlate with clinical outcomes in cancer patients undergoing ... then be employed to support the design of ...
(Date:6/24/2016)... June 24, 2016  Regular discussions on a range of ... between the two entities said Poloz. Speaking at ... Ottawa , he pointed to the country,s inflation target, ... government. "In certain ... institutions have common economic goals, why not sit down and ...
(Date:6/24/2016)... ... June 24, 2016 , ... While the majority of ... the Cary 5000 and the 6000i models are higher end machines that use the ... of the spectrophotometer’s light beam from the bottom of the cuvette holder. , ...
Breaking Biology Technology: