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Logo of jbcThe Journal of Biological Chemistry
J Biol Chem. 2013 December 27; 288(52): 36787.
PMCID: PMC3873538

Role of Frataxin, a Protein Implicated in Friedreich Ataxia, in Making Iron-Sulfur Clusters♦

Frataxin Directly Stimulates Mitochondrial Cysteine Desulfurase by Exposing Substrate-binding Sites, and a Mutant Fe-S Cluster Scaffold Protein with Frataxin-bypassing Ability Acts Similarly

♦ See referenced article, J. Biol. Chem. 2013, 288, 36773–36786

Frataxin is a mitochondrial protein involved in making iron-sulfur clusters. Deficiencies in frataxin lead to the disease Friedreich ataxia, but frataxin's precise role in Fe-S cluster biogenesis is unclear. The sulfur required for Fe-S cluster synthesis is derived from the amino acid cysteine by the cysteine desulfurase activity of Nfs1. In this Paper of the Week, Debkumar Pain at Rutgers University and colleagues used purified proteins and isolated mitochondria to show that the yeast frataxin homolog stimulates the binding of cysteine to Nfs1. The yeast version of frataxin enhances cysteine binding by inducing a conformational change in Nfs1 and exposing the substrate-binding sites. The investigators went on to demonstrate that the Fe-S cluster scaffold protein with a point mutation bypassed frataxin's function to stimulate cysteine binding to Nfs1. The authors concluded that their work “may help develop a drug for treating Friedreich ataxia associated with frataxin deficiency.”

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Model for two-tier regulation of persulfide formation by Nfs1.

Articles from The Journal of Biological Chemistry are provided here courtesy of American Society for Biochemistry and Molecular Biology