Partial conservation of functions between eukaryotic frataxin and the Escherichia coli frataxin homolog CyaY.
Frataxin is a mitochondrial protein structurally conserved from bacteria to humans. Eukaryotic frataxins are known to be involved in the maintenance of mitochondrial iron balance via roles in iron delivery and iron detoxification. The prokaryotic frataxin homolog, CyaY, has been shown to bind and donate iron for the assembly of [2Fe-2S] clusters in vitro. However, in contrast to the severe phenotypes associated with the partial or complete loss of frataxin in humans and other eukaryotes, deletion of the cyaY gene does not cause any obvious alteration of iron balance in bacterial cells, an effect that probably reflects functional redundancy between CyaY and other bacterial proteins. To study CyaY function in a nonredundant setting, we have expressed a mitochondria-targeted form of CyaY in a Saccharomyces cerevisiae strain depleted of the endogenous yeast frataxin protein (yfh1Delta). We show that in this strain CyaY complements to a large extent the loss of iron-sulfur cluster enzyme activities and heme synthesis, and thereby maintains a nearly normal respiratory growth. In addition, CyaY effectively protects yfh1Delta from oxidative damage during treatment with hydrogen peroxide but is less efficient in detoxifying excess labile iron during aerobic growth.
Bedekovics
Tibor
T
Department of Biochemistry and Medical Chemistry, Faculty of Medicine, University of Pécs, Pécs, Hungary. tibor.bedekovics@aok.pte.hu
Gajdos
Gabriella B
GB
Kispal
Gyula
G
Isaya
Grazia
G
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology*; D029968:Escherichia coli Proteins; D017353:Gene Deletion; D005816:Genetic Complementation Test; D006418:Heme / Q000096:biosynthesis; D006861:Hydrogen Peroxide / Q000633:toxicity; D007501:Iron / Q000378:metabolism; D033862:Iron-Binding Proteins / Q000235:genetics / Q000502:physiology*; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D000096923:Frataxin
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D006418:Heme; D006861:Hydrogen Peroxide; D007501:Iron; D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins; D000096923:Frataxin; C120906:CyaY protein, E coli