YFH1/YDL120W Summary Help

Standard Name YFH1 1, 2
Systematic Name YDL120W
Feature Type ORF, Verified
Description Mitochondrial matrix iron chaperone; oxidizes and stores iron; interacts with Isu1p to promote Fe-S cluster assembly; mutation results in multiple Fe/S-dependent enzyme deficiencies; human frataxin homolog is mutated in Friedrich's ataxia (2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and see Summary Paragraph)
Name Description Yeast Frataxin Homolog 1, 2
Chromosomal Location
ChrIV:245923 to 246447 | ORF Map | GBrowse
Gene Ontology Annotations All YFH1 GO evidence and references
  View Computational GO annotations for YFH1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 7 genes
Classical genetics
reduction of function
Large-scale survey
reduction of function
127 total interaction(s) for 95 unique genes/features.
Physical Interactions
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 13
  • Co-crystal Structure: 2
  • Co-fractionation: 4
  • Reconstituted Complex: 7
  • Two-hybrid: 4

Genetic Interactions
  • Dosage Lethality: 1
  • Dosage Rescue: 5
  • Negative Genetic: 52
  • Phenotypic Enhancement: 3
  • Phenotypic Suppression: 4
  • Positive Genetic: 14
  • Synthetic Growth Defect: 7
  • Synthetic Lethality: 4
  • Synthetic Rescue: 6

Expression Summary
Length (a.a.) 174
Molecular Weight (Da) 19,490
Isoelectric Point (pI) 5.69
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrIV:245923 to 246447 | ORF Map | GBrowse
Last Update Coordinates: 2004-02-11 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..525 245923..246447 2004-02-11 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000002278

Yfh1p is a mitochondrial matrix protein (3) that functions as an iron chaperone (10, 11). Yfh1p binds ferrous iron (12, 13) and couples protein assembly with iron oxidation and storage (14, 11). Yfh1p is specifically involved in the biosynthesis of iron-sulfur (Fe/S) clusters (7, 8, 9, 6), a prosthetic group required for the function of mitochondrial respiratory chain complexes, aconitase of the citric acid cycle, proteins involved in cofactor biosynthesis and many others (reviewed in 15, 16). YFH1 interacts with several genes (ISU1, NFS1, NFU1, SSQ1, ISA1, and ISA2) involved in either the synthesis of the Fe/S scaffold or its subsequent transfer to apoprotein targets (17, 9, 8). There are also ferrous iron regulated physical interactions between Yfh1p and the core Fe/S assembly complex (Isu1p/Nfs1p) (9). Yfh1p is essential for de novo Fe/S cluster assembly on Isu1p, suggesting a direct role in the incorporation of iron into Fe/S clusters (9).

YFH1, the yeast frataxin (OMIM) homolog, was originally identified based on its similarity to the human FRDA gene (5, 2, 1). Mutations in the human gene result in Friedreich's ataxia (OMIM), a disease characterized by neurodegeneration, cardiomyopathy, and diabetes (5). Frataxin is evolutionarily conserved with similar genes in worms, flies and mammals (18).

Deletion of YFH1 results in yeast strains with severe mitochondrial defects including the inability to grow on non-fermentable carbon sources (respiratory deficiency) (2, 1, 19), constitutive induction of high-affinity iron uptake, and an increase in both mitochondrial (10-fold) and cellular (2-fold) iron content that results in hypersensitivity to oxidative stress (2, 19). Increased oxidative stress results in mitochondrial DNA damage and loss (1, 2, 19), nuclear DNA damage, increased sensitivity to DNA damaging agents (20) and lifespan reduction (21). Multiple Fe/S-dependent enzyme deficiencies have been observed (aconitrase, biotin synthase, ferrochelatase, and respiratory chain complexes) in null mutants (4, 6, 22, 23). Many of these defects are shared by cells derived from Friedreich's ataxia patients (4, 24). In addition, defects associated with yfh1 null mutants can be rescued by expression of either the full-length human gene (25, 26) or chimeric constructs containing the YFH1-homologous domain, but not disease-associated missense constructs (1), suggesting conservation of function.

Last updated: 2008-10-03 Contact SGD

References cited on this page View Complete Literature Guide for YFH1
1) Wilson RB and Roof DM  (1997) Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the frataxin homologue. Nat Genet 16(4):352-7
2) Babcock M, et al.  (1997) Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science 276(5319):1709-12
3) Branda SS, et al.  (1999) Yeast and human frataxin are processed to mature form in two sequential steps by the mitochondrial processing peptidase. J Biol Chem 274(32):22763-9
4) Rotig A, et al.  (1997) Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia. Nat Genet 17(2):215-7
5) Campuzano V, et al.  (1996) Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271(5254):1423-7
6) Chen OS, et al.  (2002) Inhibition of Fe-S cluster biosynthesis decreases mitochondrial iron export: evidence that Yfh1p affects Fe-S cluster synthesis. Proc Natl Acad Sci U S A 99(19):12321-6
7) Muhlenhoff U, et al.  (2003) Components involved in assembly and dislocation of iron-sulfur clusters on the scaffold protein Isu1p. EMBO J 22(18):4815-25
8) Ramazzotti A, et al.  (2004) Mitochondrial functional interactions between frataxin and Isu1p, the iron-sulfur cluster scaffold protein, in Saccharomyces cerevisiae. FEBS Lett 557(1-3):215-20
9) Gerber J, et al.  (2003) An interaction between frataxin and Isu1/Nfs1 that is crucial for Fe/S cluster synthesis on Isu1. EMBO Rep 4(9):906-11
10) Bulteau AL, et al.  (2004) Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity. Science 305(5681):242-5
11) Park S, et al.  (2003) Yeast frataxin sequentially chaperones and stores iron by coupling protein assembly with iron oxidation. J Biol Chem 278(33):31340-51
12) Adamec J, et al.  (2000) Iron-dependent self-assembly of recombinant yeast frataxin: implications for Friedreich ataxia. Am J Hum Genet 67(3):549-62
13) Cook JD, et al.  (2006) Monomeric yeast frataxin is an iron-binding protein. Biochemistry 45(25):7767-77
14) Park S, et al.  (2002) The ferroxidase activity of yeast frataxin. J Biol Chem 277(41):38589-95
15) Johnson DC, et al.  (2005) Structure, function, and formation of biological iron-sulfur clusters. Annu Rev Biochem 74:247-81
16) Lill R and Muhlenhoff U  (2008) Maturation of iron-sulfur proteins in eukaryotes: mechanisms, connected processes, and diseases. Annu Rev Biochem 77:669-700
17) Aloria K, et al.  (2004) Iron-induced oligomerization of yeast frataxin homologue Yfh1 is dispensable in vivo. EMBO Rep 5(11):1096-101
18) Huynen MA, et al.  (2001) The phylogenetic distribution of frataxin indicates a role in iron-sulfur cluster protein assembly. Hum Mol Genet 10(21):2463-8
19) Foury F and Cazzalini O  (1997) Deletion of the yeast homologue of the human gene associated with Friedreich's ataxia elicits iron accumulation in mitochondria. FEBS Lett 411(2-3):373-7
20) Karthikeyan G, et al.  (2002) The mitochondrial protein frataxin prevents nuclear damage. Hum Mol Genet 11(11):1351-62
21) Desmyter L, et al.  (2004) Expression of the human ferritin light chain in a frataxin mutant yeast affects ageing and cell death. Exp Gerontol 39(5):707-15
22) Muhlenhoff U, et al.  (2002) Characterization of iron-sulfur protein assembly in isolated mitochondria. A requirement for ATP, NADH, and reduced iron. J Biol Chem 277(33):29810-6
23) Lange H, et al.  (2004) The heme synthesis defect of mutants impaired in mitochondrial iron-sulfur protein biogenesis is caused by reversible inhibition of ferrochelatase. J Biol Chem 279(28):29101-8
24) Bradley JL, et al.  (2000) Clinical, biochemical and molecular genetic correlations in Friedreich's ataxia. Hum Mol Genet 9(2):275-82
25) Cavadini P, et al.  (2000) Human frataxin maintains mitochondrial iron homeostasis in Saccharomyces cerevisiae. Hum Mol Genet 9(17):2523-30
26) Campanella A, et al.  (2004) The expression of human mitochondrial ferritin rescues respiratory function in frataxin-deficient yeast. Hum Mol Genet 13(19):2279-88