Copper redox chemistry of plant frataxins

The presence of a conserved cysteine residue in the C-terminal amino acid sequences of plant frataxins differentiates these frataxins from those of other kingdoms and may be key in frataxin assembly and function. We report a full study on the ability of Arabidopsis (AtFH) and Zea mays (ZmFH-1 and ZmFH-2) frataxins to assemble into disulfide-bridged dimers by copper-driven oxidation and to revert to monomers by chemical reduction. We monitored the redox assembly-disassembly process by electrospray ionization mass spectrometry, electrophoresis, UV–Vis spectroscopy, and fluorescence measurements. We conclude that plant frataxins AtFH, ZmFH-1 and ZmFH-2 are oxidized by Cu2+ and exhibit redox cysteine monomer – cystine dimer interexchange. Interestingly, the tendency to interconvert is not the same for each protein. Through yeast phenotypic rescue experiments, we show that plant frataxins are important for plant survival under conditions of excess copper, indicating that these proteins might be involved in copper metabolism. The first study on copper chemistry of plant frataxins reveals the existence of a reversible monomer-disulfide dimer interconversion never before seen in these proteins. [Display omitted] •Plant frataxins contain a Cys residue that may be key in their assembly and function.•Plant frataxins assemble into disulfide-bridged dimers by copper-driven oxidation.•Disulfide-bridged dimers of plant frataxins revert to monomers by chemical reduction.•Plant frataxins exhibit different redox Cys monomer - cystine dimer interexchange.•Plant frataxins are important for plant survival under conditions of excess copper.