New gene discovered that regulates protein haemoglobin

The biochemical community can celebrate with the discovery of a new gene that regulates haemoglobin synthesis throughout the development of red blood cells.

This new discovery will help scientists better understand and treat human anemias and mitochondrial disorders.

Anemia is a condition where blood has a lower than normal number of red blood cells (or haemoglobin levels).

It can affect anyone at any age, however women of child bearing age and older people are at increased risk. Babies and children might also be at higher risk due to nutritional iron deficiency or lead poisoning.

Using an unbiased zebrafish genetic screen to clone mitochondrial ATPase inhibitory factor-1 gene, or Atpif1, researchers at Brigham and Women's Hospital (BWH) have found that the gene enables animals (such as mice, humans, zebrafish) to produce haemoglobin.

Haemoglobin is the protein in red cells blood cells that move oxygen within the blood.

The researchers discovered that severe anemia occurs when there is a loss of Atpif1.

They also found that the gene, Atpif1, also controls the enzymatic action of ferrochelatase, or Fech. 

Fech is the terminal enzyme in heme (a part of haemoglobin) production.

"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, the study's first author from the Department of Medicine at the university.

The Atpif1 gene is important for normal red blood cell differentiation and a lack of it in humans could lead to diseases such as congenital sideroblastic anemias and other conditions linked to dysfunctional mitochondria.

"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, the senior author of the study from the university.

The researchers continue to search for and discover new genes that are responsible for hematopoietic stem cell formation and red cell differentiation.

These discoveries have led to a better understanding of human congenital anemias and opportunities for more effective treatments for patients.

Posted by Ben Evans