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Review
. 2016 Jun:38:45-51.
doi: 10.1016/j.gde.2016.03.006. Epub 2016 Apr 7.

Roles of Fe-S proteins: from cofactor synthesis to iron homeostasis to protein synthesis

Debkumar Pain  1 , Andrew Dancis  2
Affiliations
Review

Roles of Fe-S proteins: from cofactor synthesis to iron homeostasis to protein synthesis

Debkumar Pain et al. Curr Opin Genet Dev. 2016 Jun.

Abstract

Fe-S cluster assembly is an essential process for all cells. Impairment of Fe-S cluster assembly creates diseases in diverse and surprising ways. In one scenario, the loss of function of lipoic acid synthase, an enzyme with Fe-S cluster cofactor in mitochondria, impairs activity of various lipoamide-dependent enzymes with drastic consequences for metabolism. In a second scenario, the heme biosynthetic pathway in red cell precursors is specifically targeted, and iron homeostasis is perturbed, but lipoic acid synthesis is unaffected. In a third scenario, tRNA modifications arising from action of the cysteine desulfurase and/or Fe-S cluster proteins are lost, which may lead to impaired protein synthesis. These defects can then result in cancer, neurologic dysfunction or type 2 diabetes.

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Figures

Fig. 1
Fig. 1
Linkage of Fe-S cluster assembly defects and MMDS multiple mitochondrial dysfunction syndrome. Details are included in the text.
Fig. 2
Fig. 2
Schematic showing possible causation of acquired sideroblastic anemia. Upper panel: normal hematopoiesis. Lower panel: SF3B1 K700E allele in a bone marrow stem cell causes altered splicing of ABCB7, non-sense mediated decay, and ring sideroblast formation in red cell precursors. Red cell precursors expand in the bone marrow but viable circulating red cells are decreased (ineffective erythropoiesis).
See this image and copyright information in PMC

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