Reactome | Frataxin binds iron

Frataxin binds iron

Stable Identifier

R-HSA-1362416

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial matrix

ReviewStatus

5/5

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Frataxin (FXN) specifically binds 2 atoms of ferrous iron per monomer (reviewed in Stemmler et al. 2010). Iron bound to Frataxin may (Yoon and Cowan 2003, Gerber et al. 2003) or may not (Schmucker et al. 2011) enhance the interaction of Frataxin with NFS1, ICSU, and ISD11. Frataxin was shown to stimulate the cysteine desulfurase activity of NFS1 and was proposed to be a regulator of sulfur production (Tsai et al. 2010). The formation of sulfide by NFS1 is most efficiently observed when NFS1 is in complex with ISD11, ISCU, and FXN in the presence of cysteine and iron. This means that only the complete system of NFS1, ISD11, ISCU, FXN, cysteine, and iron is fully active as a desulfurase. FXN therefore seems to be a regulator of the cysteine desulfurase permitting sulfide production only when all components needed for Fe-S cluster synthesis are present and the ISCU-bound Fe-S cluster can be formed.

Literature References

PubMed ID	Title	Journal	Year
12785837	Iron-sulfur cluster biosynthesis. Characterization of frataxin as an iron donor for assembly of [2Fe-2S] clusters in ISU-type proteins Yoon, T, Cowan, JA	J Am Chem Soc	2003
21776984	Structure-function analysis of Friedreich's ataxia mutants reveals determinants of frataxin binding and activation of the Fe-S assembly complex Bridwell-Rabb, J, Winn, AM, Barondeau, DP	Biochemistry	2011
21298097	Mammalian frataxin: an essential function for cellular viability through an interaction with a preformed ISCU/NFS1/ISD11 iron-sulfur assembly complex Schmucker, S, Martelli, A, Colin, F, Page, A, Wattenhofer-Donzé, M, Reutenauer, L, Puccio, H	PLoS One	2011
11823441	Assembly and iron-binding properties of human frataxin, the protein deficient in Friedreich ataxia Cavadini, P, O'Neill, HA, Benada, O, Isaya, G	Hum Mol Genet	2002
20873749	Human frataxin is an allosteric switch that activates the Fe-S cluster biosynthetic complex Tsai, CL, Barondeau, DP	Biochemistry	2010
20522547	Frataxin and mitochondrial FeS cluster biogenesis Stemmler, TL, Lesuisse, E, Pain, D, Dancis, A	J Biol Chem	2010
18425540	Mapping iron binding sites on human frataxin: implications for cluster assembly on the ISU Fe-S cluster scaffold protein Huang, J, Dizin, E, Cowan, JA	J Biol Inorg Chem	2008
15509595	Iron-sulfur protein maturation in human cells: evidence for a function of frataxin Stehling, O, Elsässer, HP, Brückel, B, Mühlenhoff, U, Lill, R	Hum. Mol. Genet.	2004