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Researchers Identify Gene Which Regulates Heme Synthesis

November 20, 2012


A team of researchers led by Dr. Dhvanit Shah of Harvard Medical School has shown that mitochondrial ATPase inhibitory factor 1 (Atpif1) plays an important role in regulating heme synthesis in red blood cells. Using genetic complementation studies in a zebrafish mutant model, the researchers found that Atpif1 affects heme synthesis through its impact on the catalytic efficiency of ferrochelatase, the terminal enzyme in the heme biosynthesis pathway. Deficient Atpif1 causes changes in the mitochondrial pH and redox potential, which are sensed by the 2-iron, 2-sulfer cluster of ferrochelatase. The ferrochelatase enzyme then responds to these metabolic changes by reducing heme synthesis. The elucidation of this mechanism may have important implications for understanding and treating human congenital anemias.   

 

 

Reference

1.     Shah DI, Takahashi-Makise N, Cooney JD, Li L, Schultz IJ, Pierce EL, Narla A, Seguin A, Hattangadi SM, Medlock AE, Langer NB, Dailey TA, Hurst SN, Faccenda D, Wiwczar JM, Heggers SK, Vogin G, Chen W, Chen C, Campagna DR, Brugnara C, Zhou Y, Ebert BL, Danial NN, Fleming MD, Ward DM, Campanella M, Dailey HA, Kaplan J, Paw BH. Mitochondrial Atpif1 regulates haem synthesis in developing erythroblasts. Nature 2012.

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