Matching Supply and Demand

+ See all authors and affiliations

Science  24 Apr 2009:
Vol. 324, Issue 5926, pp. 440
DOI: 10.1126/science.324_440b

In humans, a deficiency of the mitochondrial protein frataxin leads to Friedreich's ataxia, a progressive and fatal neurodegenerative disease. Frataxin has been implicated in heme metabolism and in the assembly of Fe-S clusters. In particular, it has been proposed to act as either an iron chaperone or an iron-storage protein.

Adinolfi et al. propose that in Escherichia coli, frataxin fine-tunes the flux of Fe-S cluster synthesis. Using absorbance and CD spectroscopy, they showed that the bacterial frataxin ortholog CyaY (green in the above schematic) inhibits the formation of Fe-S clusters on the scaffold protein IscU (gray). Clusters are synthesized on IscU when iron (red) combines with sulfur (yellow) that has been extracted from cysteine by the disulfurase IscS (blue); IscU then inserts the clusters into the final acceptors. CyaY did not interfere with the transfer of assembled clusters from IscU to the acceptor ferredoxin and also did not affect the ability of IscS to convert cysteine to alanine. Fluorescence and NMR data revealed that CyaY did not compete with IscU for binding to IscS and that the IscS-binding surface of CyaY mapped to its iron-binding region. Mutants designed to disrupt the iron-binding capacity of CyaY reduced its inhibitory effect. The authors suggest that frataxins are iron sensors that interact with the IscS-IscU system at high iron concentrations and restrict the supply of clusters in the absence of needy acceptors.

Nat. Struct. Mol. Biol. 16, 390 (2009).

Navigate This Article