Turning Saccharomyces cerevisiae into a Frataxin-Independent Organism

• DOI: 10.1371/journal.pgen.1005135
• Publication Date: 2015-05-21T18:07:53Z
• Authors: Heeyong Yoon; Simon A. B. Knight; Alok Pandey; Jayashree Pain; Serdar Turkarslan; Debkumar Pain; Andrew Dancis
• Keywords: Frataxin; Iron–sulfur cluster

Frataxin (Yfh1 in yeast) is a conserved protein and deficiency leads to the neurodegenerative disease Friedreich's ataxia. critical for Fe-S cluster assembly mitochondria, interacting with other components of machinery, including cysteine desulfurase Nfs1, Isd11 Isu1 scaffold protein. Yeast methionine isoleucine substitution (M141I), which E. coli amino acid inserted at this position, corrected most phenotypes that result from lack Yfh1 yeast. This suppressor behaved as genetic dominant. Furthermore frataxin-bypass activity required completely functional Nfs1 correlated presence efficient function. A screen random mutations identified only M141 substitutions, Ile, Cys, Leu, or Val. In each case, mitochondrial persulfide formation was enhanced, improved absence frataxin. Direct targeting entire IscU ∆yfh1 mitochondria also ameliorated mutant phenotypes. contrast, expression reverse i.e. Ile Met change led worsening phenotypes, severely compromised growth, increased sensitivity oxygen, clusters heme, impaired iron homeostasis. bioinformatic survey eukaryotic Isu1/prokaryotic database entries sorted on utilized position unique groupings, virtually all scaffolds using Met, preponderance prokaryotic acids. The frataxin-bypassing acids Val, were found predominantly prokaryotes. 141 Isu1, effect likely mimics ancient feature machinery.