Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the frataxin homologue.
Friedreich's ataxia (FRDA) is an autosomal recessive degenerative disorder that primarily affects the nervous system and heart. Patients with FRDA have point mutations or trinucleotide repeat expansions in both alleles of FRDA, which encodes a protein termed frataxin. We show that the yeast frataxin homologue, which we have named YFH1, localizes to mitochondria and is required to maintain mitochondrial DNA. The YFH1-homologous domain of frataxin functions in yeast and a disease-associated missense mutation of this domain, or the corresponding domain in YFH1, reduces function. Our data suggest that mitochondrial dysfunction contributes to FRDA pathophysiology.
Wilson
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RB
Department of Pathology, University of Pennsylvania, Philadelphia 19104, USA. WilsonR@mail.med.upenn.edu
Roof
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DM
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003001:Cloning, Molecular; D004271:DNA, Fungal / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D005621:Friedreich Ataxia / Q000235:genetics; D017353:Gene Deletion; D005816:Genetic Complementation Test; D033862:Iron-Binding Proteins; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D000096923:Frataxin
D004271:DNA, Fungal; D004272:DNA, Mitochondrial; D033862:Iron-Binding Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D000096923:Frataxin