Researchers at Brigham and Women's Hospital (BWH) have discovered a new gene that regulates hemoglobin synthesis during red blood cell formation. The findings advance the biomedical community's understanding and treatment of human anemias and mitochondrial disorders.
The study will be published online on November 7, 2012 in Nature.
The researchers used an unbiased zebrafish genetic screen to clone mitochondrial ATPase inhibitory factor-1 gene, or Atpif1. The gene allows animals—zebrafish, mice and humans for instance—to efficiently make hemoglobin. Hemoglobin is the protein in red blood cells responsible for transporting oxygen in the blood.
The researchers found that loss of Atpif1 causes severe anemia. Moreover, the researchers uncovered a broader mechanistic role for Atpif1—regulating the enzymatic activity of ferrochelatase, or Fech. Fech is the terminal enzyme in heme (a component of hemoglobin) synthesis.
"Our study has established a unique functional link between Atpif1-regulated mitochondrial pH, redox potential, and [2Fe-2S] cluster binding to Fech in modulating its heme synthesis," said Dhvanit Shah, PhD, BWH Division of Hematology, Department of Medicine, first study author.
The researchers were also able to produce data on the human version of Atpif1, noting its functional importance for normal red blood cell differentiation, and noting that a deficiency may contribute to human diseases, such as congenital sideroblastic anemias and other diseases related to dysfunctional mitochondria (the energy powerhouses of cells).
"Discovering the novel mechanism of Atpif1 as a regulator of heme synthesis advances the understanding of mitochondrial heme homeostasis and red blood cell development," said Barry Paw, MD, PhD, BWH Division of Hematology, Department of Medicine, senior study author.
Shah and Paw continue to identify new genes responsible for hematopoietic stem cell development and red cell differentiation. Their identification of new genes will elucidate the new mechanisms regulating hematopoiesis—the formation of blood cell components. Their work not only provides greater insight into human congenital anemias, but also new opportunities for improved therapies.
Brigham and Women's Hospital: http://www.brighamandwomens.org
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Results of largest ever genetics study of a single population could also help refine dates for major events during human evolution Humans are evolving more rapidly than previously thought, according to the largest ever genetics study of a single population.
Latest genetic tests reveal another break in the male line, potentially undermining the legitimacy of the entire House of Plantagenet When scientists revealed last year that an adulterous affair had apparently broken the male line in Richard III’s family tree, they vowed to investigate further.
By 2016, Icelandic genetics company deCODE will have data on half the country's population. Releasing the data will be controversial, but could save lives
A clinical trial has shown that the drug aducanumab slows cognitive decline in people with Alzheimer's and reduces the amount of amyloid plaque in their brain
A leading researcher issues a call for pills that deliver a full course of treatment in one swallow.One of the world’s preëminent biomedical researchers is calling for a concerted effort by scientists to develop pills that would stay in the stomach or gut for weeks or months once swallowed, delivering one or more drugs continuously or over set intervals.
Two genes responsible for building up drug-resistance can easily be shared between a family of bacteria
When malaria parasites infect blood, they manufacture odor molecules that smell sweet to mosquitoes, scientists report. So how do these odors get from the bloodstream to the insects?
Researchers are developing new method of wireless deep brain stimulation.
Zoos belonging to World Association of Zoos and Aquariums filmed allowing shocking mistreatment of elephants, dolphins, lions, bears, penguins and whales
Owners of Highland Wildlife Park hope Victoria, 18, will get chummy with male Arktos during her stay in the Cairngorms