Iron-induced oligomerization of yeast frataxin homologue Yfh1 is dispensable in vivo.
The neurodegenerative disease Friedreich's ataxia is caused by reduced levels of frataxin, a mitochondrial matrix protein. The in vivo role of frataxin is under debate. Frataxin, as well as its yeast homologue Yfh1, binds multiple iron atoms as an oligomer and has been proposed to function as a crucial iron-storage protein. We identified a mutant Yfh1 defective in iron-induced oligomerization. This mutant protein was able to replace functionally wild-type Yfh1, even when expressed at low levels, when mitochondrial iron levels were high and in mutant strains having deletions of genes that had synthetic growth defects with a YFH1 deletion. The ability of an oligomerization-deficient Yfh1 to function in vivo suggests that oligomerization, and thus oligomerization-induced iron storage, is not a critical function of Yfh1. Rather, the capacity of this oligomerization-deficient mutant to interact with the Isu protein suggests a more direct role of Yfh1 in iron-sulphur cluster biogenesis.
Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, Wisconsin 53706, USA.
Kerman
K
Aloria
Brenda
B
Schilke
Amy
A
Andrew
Elizabeth A
EA
Craig
D000595:Amino Acid Sequence; D000818:Animals; D000838:Anions; D004926:Escherichia coli / Q000378:metabolism; D017353:Gene Deletion; D006238:Haploidy; D006801:Humans; D007501:Iron / Q000737:chemistry / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D007506:Iron-Sulfur Proteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae; D000096923:Frataxin
D000838:Anions; D007501:Iron; D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins; D000096923:Frataxin