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Advances in Hematology
Volume 2010, Article ID 329394, 8 pages
http://dx.doi.org/10.1155/2010/329394
Review Article

Erythropoiesis and Iron Sulfur Cluster Biogenesis

Molecular Medicine Program, Eunice Kennedy Shriver National Institutes of Child Health and Human Development at (NIH), 9000 Rockville Pike, Bethesda, MD 20892, USA

Received 1 March 2010; Revised 4 June 2010; Accepted 2 August 2010

Academic Editor: Maria R. Baer

Copyright © 2010 Hong Ye and Tracey A. Rouault. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Erythropoiesis in animals is a synchronized process of erythroid cell differentiation that depends on successful acquisition of iron. Heme synthesis depends on iron through its dependence on iron sulfur (Fe-S) cluster biogenesis. Here, we review the relationship between Fe-S biogenesis and heme synthesis in erythropoiesis, with emphasis on the proteins, GLRX5, ABCB7, ISCA, and C1orf69. These Fe-S biosynthesis proteins are highly expressed in erythroid tissues, and deficiency of each of these proteins has been shown to cause anemia in zebrafish model. GLRX5 is involved in the production and ABCB7 in the export of an unknown factor that may function as a gauge of mitochondrial iron status, which may indirectly modulate activity of iron regulatory proteins (IRPs). ALAS2, the enzyme catalyzing the first step in heme synthesis, is translationally controlled by IRPs. GLRX5 may also provide Fe-S cofactor for ferrochelatase, the last enzyme in heme synthesis. ISCA and C1orf69 are thought to assemble Fe-S clusters for mitochondrial aconitase and for lipoate synthase, the enzyme producing lipoate for pyruvate dehydrogenase complex (PDC). PDC and aconitase are involved in the production of succinyl-CoA, a substrate for heme biosynthesis. Thus, many steps of heme synthesis depend on Fe-S cluster assembly.