Researchers Found a Genetic Reason of Anemia-Atpifl

Loss of Atpifl gene might cause anemia

Anemia can affect people of all ages. It is a condition in which people’s blood has a lower number of red blood cells or hemoglobin levels than normal. Women of childbearing age and older adults are at higher risk. Babies and children are also at risk for anemia due to nutritional iron deficiency or lead poisoning.

On November 7, 2012 Nature Journal, researchers of Brigham and Women’s Hospital (BWH) published their research achievement on anemia. They have discovered a new gene that regulates hemoglobin synthesis during red blood cell formation, which could be a roadmap for treating human anemias and mitochondrial disorders.

In the study, researchers used an unbiased zebrafish genetic screen to clone mitochondrial ATPase inhibitory factor-1 gene, or Atpif1. The gene allows organism, such as zebrafish, mice and humans to efficiently make hemoglobin, a protein in red blood cells transporting oxygen for blood. They were 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. They found that loss of Atpif1 causes severe anemia. They also uncovered a broader mechanistic role for Atpif1—regulating the enzymatic activity of ferrochelatase, or Fech which is the terminal enzyme in heme synthesis.

The first study author, PhD Dhvanit Shah said, "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".

The senior study author, PhD Barry Paw said, "Discovering the novel mechanism of Atpif1 as a regulator of heme synthesis advances the understanding of mitochondrial heme homeostasis and red blood cell development".

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. Their work not only provides greater insight into human congenital anemias, but also new opportunities for improved therapies.