J-domain Protein, Jac1p, of Yeast Mitochondria Required for Iron Homeostasis and Activity of Fe-S Cluster Proteins

Abstract

J-proteins are molecular chaperones with a characteristic domain predicted to mediate interaction with Hsp70 proteins. We have previously isolated yeast mutants of the mitochondrial Hsp70, Ssq1p, in a genetic screen for mutants with altered iron homeostasis. Here we describe the isolation of mutants of the J-domain protein, Jac1p, using the same screen. Mutantjac1 alleles predicted to encode severely truncated proteins (lacking 70 or 152 amino acids) were associated with phenotypes strikingly similar to the phenotypes of ssq1mutants. These phenotypes include activation of the high affinity cellular iron uptake system and iron accumulation in mitochondria. In contrast to iron accumulation, Fe-S proteins of mitochondria were specifically deficient. In jac1 mutants, like inssq1 mutants, processing of the Yfh1p precursor protein from intermediate to mature forms was delayed. In the genetic backgrounds used in this study, jac1 null mutants were found to be viable, permitting analysis of genetic interactions. TheΔjac1 Δssq1 double mutant was more severely compromised for growth than either single mutant, suggesting a synthetic or additive effect of these mutations. Overexpression of Jac1p partially suppressed ssq1 slow growth and vice versa. Similar mitochondrial localization and similar mutant phenotypes suggest that Ssq1p and Jac1p are functional partners in iron homeostasis. J-proteins are molecular chaperones with a characteristic domain predicted to mediate interaction with Hsp70 proteins. We have previously isolated yeast mutants of the mitochondrial Hsp70, Ssq1p, in a genetic screen for mutants with altered iron homeostasis. Here we describe the isolation of mutants of the J-domain protein, Jac1p, using the same screen. Mutantjac1 alleles predicted to encode severely truncated proteins (lacking 70 or 152 amino acids) were associated with phenotypes strikingly similar to the phenotypes of ssq1mutants. These phenotypes include activation of the high affinity cellular iron uptake system and iron accumulation in mitochondria. In contrast to iron accumulation, Fe-S proteins of mitochondria were specifically deficient. In jac1 mutants, like inssq1 mutants, processing of the Yfh1p precursor protein from intermediate to mature forms was delayed. In the genetic backgrounds used in this study, jac1 null mutants were found to be viable, permitting analysis of genetic interactions. TheΔjac1 Δssq1 double mutant was more severely compromised for growth than either single mutant, suggesting a synthetic or additive effect of these mutations. Overexpression of Jac1p partially suppressed ssq1 slow growth and vice versa. Similar mitochondrial localization and similar mutant phenotypes suggest that Ssq1p and Jac1p are functional partners in iron homeostasis. open reading frame polymerase chain reaction succinate dehydrogenase matrix processing peptidase base pair(s) kilobase pair(s) p-iodonitrotetrazolium violet Iron is required as a cofactor for critical proteins involved in diverse biological processes including oxidation-reduction, cellular respiration, oxygen interaction, and metabolic conversions (1Brittenham G. Hoffman R. Benz E. Shattil S. Furie B. Cohen H. Silberstein L. McGlave P. Hematology: Basic Principles and Practice.in: Churchill Livingstone, Philadelphia2000: 397-428Google Scholar). However, iron can also be extremely toxic. The toxicity of iron results from interaction with reactive oxygen intermediates, generating highly toxic hydroxyl radicals that damage nearby macromolecules, including lipids, DNA, and proteins (2Halliwell B. Gutteridge J.M.C. Free Radicals in Biology and Medicine. Clarendon, Oxford, United Kingdom1991Google Scholar). Cells cope with this dual nature of iron in part by homeostatic regulation of cellular iron uptake. InSaccharomyces cerevisiae and other organisms, iron uptake is induced by iron deprivation and repressed by iron sufficiency (3Askwith C.C. de Silva D. Kaplan J. Mol. Microbiol. 1996; 20: 27-34Crossref PubMed Scopus (103) Google Scholar). The components of the iron uptake system of yeast include a surface reductase encoded by FRE1 that is regulated by iron levels through changes in its transcription (4Dancis A. Roman D.G. Anderson G.J. Hinnebusch A.G. Klausner R.D. Proc. Natl. Acad. Sci. U. S. A. 1992; 89: 3869-3873Crossref PubMed Scopus (282) Google Scholar). We used this property of theFRE1 gene to select mutants that failed to repressFRE1 expression in response to iron. The types of mutants selected included mutants with perturbed cellular iron uptake (5Dancis A. Yuan D.S. Haile D. Askwith C. Eide D. Moehle C. Kaplan J. Klausner R.D. Cell. 1994; 76: 393-402Abstract Full Text PDF PubMed Scopus (567) Google Scholar, 6Stearman R. Yuan D.S. Yamaguchi-Iwai Y. Klausner R.D. Dancis A. Science. 1996; 271: 1552-1557Crossref PubMed Scopus (582) Google Scholar), iron sensing (7Yamaguchi-Iwai Y. Dancis A. Klausner R.D. EMBO J. 1995; 14: 1231-1239Crossref PubMed Scopus (314) Google Scholar), or intracellular iron distribution (8Knight S.A. Sepuri N.B. Pain D. Dancis A. J. Biol. Chem. 1998; 273: 18389-18393Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar, 9Li J. Kogan M. Knight S. Pain D. Dancis A. J. Biol. Chem. 1999; 274: 33025-33034Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar). This last category of mutants, which included ssq1 mutants, exhibited misregulated activation of high affinity cellular iron uptake and accumulation of iron within mitochondria (8Knight S.A. Sepuri N.B. Pain D. Dancis A. J. Biol. Chem. 1998; 273: 18389-18393Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar). The SSQ1 gene encodes a low abundance Hsp70 chaperone of the mitochondrial matrix (10Schilke B. Forster J. Davis J. James P. Walter W. Laloraya S. Johnson J. Miao B. Craig E. J. Cell Biol. 1996; 134: 603-613Crossref PubMed Scopus (72) Google Scholar). We now describe the isolation of jac1 mutants with similar phenotypes using the same selection scheme. Jac1p contains a J-domain with a signature HPD (histidine, proline, aspartate) tripeptide motif (11Strain J. Lorenz C.R. Bode J. Garland S. Smolen G.A. Ta D.T. Vickery L.E. Culotta V.C. J. Biol. Chem. 1998; 273: 31138-31144Abstract Full Text Full Text PDF PubMed Scopus (169) Google predicted to mediate interaction with Craig Cell. Full Text Full Text PDF PubMed Scopus Google Scholar). Jac1p be the functional of Ssq1p with in iron the and mitochondria. Culotta and (11Strain J. Lorenz C.R. Bode J. Garland S. Smolen G.A. Ta D.T. Vickery L.E. Culotta V.C. J. Biol. Chem. 1998; 273: 31138-31144Abstract Full Text Full Text PDF PubMed Scopus (169) Google have ssq1 mutants by using a genetic screen that for growth of a yeast in of jac1 were associated with of Fe-S proteins (11Strain J. Lorenz C.R. Bode J. Garland S. Smolen G.A. Ta D.T. Vickery L.E. Culotta V.C. J. Biol. Chem. 1998; 273: 31138-31144Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar). Fe-S are in which iron and are in and to the of proteins of to or with of these are involved in biological from cellular to metabolic conversions H. J. Biol. Chem. PubMed Scopus Google Scholar). the can be Chem. 1992; Scopus Google Scholar), genetic and that in is by L. R. R. D. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, L. D. D. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar, Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, E. J. PubMed Scopus Google Scholar). In of these proteins are associated the L. D. D. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar), and biological in Fe-S are the of L. D. J. Biol. Chem. 1994; Full Text PDF PubMed Google Scholar, P. J. Johnson M. D. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, Vickery L.E. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). of Ssq1p or and Jac1p or have found the suggesting a in Fe-S or L. D. D. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google L.E. Ta D.T. Sci. PubMed Scopus Google Scholar). Overexpression of these proteins is required for of Fe-S proteins in M. Y. J. 1999; PubMed Scopus Google Scholar). In a study, Vickery and Vickery L.E. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google a interaction of the Hsp70 a and protein, a for of the Fe-S P. J. Johnson M. D. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). Here we the phenotypes of jac1 mutants with altered iron and to phenotypes We also genetic and of yeast and In was used and in other was used the the used was and from was by growth in with of with was by of iron. was and iron was from a of iron iron was with for and yeast have for in Scholar). was from by of of SSQ1 and the of was to by to a of The was and to from single These were to with and of the which were for single and The mutants from by this included and The and were used in (5Dancis A. Yuan D.S. Haile D. Askwith C. Eide D. Moehle C. Kaplan J. Klausner R.D. Cell. 1994; 76: 393-402Abstract Full Text PDF PubMed Scopus (567) Google Scholar). and were with and were of and of and In mutant selection using the mutant This a mutant of which is truncated amino of the and was previously (8Knight S.A. Sepuri N.B. Pain D. Dancis A. J. Biol. Chem. 1998; 273: 18389-18393Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar). In and open reading frame was by of a gene a in the (7Yamaguchi-Iwai Y. Dancis A. Klausner R.D. EMBO J. 1995; 14: 1231-1239Crossref PubMed Scopus (314) Google Scholar), and was of the in was with and and the were for reductase iron and the mutant iron for was as to was with the This was with the of and a with and with and was and as a for SSQ1 was in The SSQ1 gene was in the This was with and a with and was and used as a the of the were to to growth PubMed Scopus Google Scholar). The and SSQ1 were and a was by The was to the The which for was were and The were to and were for alleles using The for this analysis were as and a of and a and a and a was by a yeast P. D. PubMed Scopus Google for of the slow growth and reductase of a in the The of of and included The with of was from isolated from by using polymerase and the the and were from the and and the same of were to The and mutant with and were for the in the The was also the same in for in high levels of regulated the and truncated amino or amino were from the with and and J. Kogan M. Knight S. Pain D. Dancis A. J. Biol. Chem. 1999; 274: 33025-33034Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar). The and be with a for The SSQ1 was of the same and also be with the The was by a and and were the and of the open reading for of the with a the The be by with and A. G.J. E. J. P. 1998; 14: PubMed Scopus Google Scholar), and A. EMBO J. PubMed Scopus Google were with this and were selected for growth in the of In of the was by a with was within a SSQ1 the of of this with and was a to The a expression in the was with and and the of with in was induced by for The protein was isolated from a and with and The was by and found to a by with The was from the and used to for of The amino of the SSQ1 was in with from the of the using the as and used to J. S. Pain D. Dancis A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), and Sepuri N.B. S. Dancis A. Pain D. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google have used in included or were isolated as H. Pain D. G. J. Cell Biol. PubMed Scopus Google Scholar). The was for and the was used as a mitochondria were in the iron of or mutant yeast were to for in with of iron. of was were isolated in the and to of protein was to in for and in of for in a were in a in the of a of and Sepuri N.B. S. Dancis A. Pain D. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar). mitochondria and and Sepuri N.B. S. Dancis A. Pain D. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar). for reaction were with for The was and the were by and to of matrix processing to processing of mitochondrial precursor proteins was as S. Dancis A. Pain D. Mol. 1999; PubMed Scopus Google Scholar). affinity cellular iron uptake was as (5Dancis A. Yuan D.S. Haile D. Askwith C. Eide D. Moehle C. Kaplan J. Klausner R.D. Cell. 1994; 76: 393-402Abstract Full Text PDF PubMed Scopus (567) Google Scholar). was by the as H. J. Biol. Chem. Full Text PDF PubMed Google Scholar). dehydrogenase was mitochondria in by the of p-iodonitrotetrazolium violet to as P. J. PubMed Scopus Google Scholar). of mitochondrial proteins by and to were with and for The of and the of were by the to C. A.G. PubMed Scopus Google Scholar). FRE1 encodes the surface reductase and is required for iron from iron (4Dancis A. Roman D.G. Anderson G.J. Hinnebusch A.G. Klausner R.D. Proc. Natl. Acad. Sci. U. S. A. 1992; 89: 3869-3873Crossref PubMed Scopus (282) Google Scholar). The FRE1 which is repressed in response to was to the that failed to to were selected for to in the of iron and in the of (5Dancis A. Yuan D.S. Haile D. Askwith C. Eide D. Moehle C. Kaplan J. Klausner R.D. Cell. 1994; 76: 393-402Abstract Full Text PDF PubMed Scopus (567) Google Scholar). The selected mutants were in the SSQ1 in to more of these mutants, the screen was by of of SSQ1 in the mutants, and were selected and found to surface and high affinity iron uptake. The mutant phenotypes were found to be The mutants were with a and the slow growth and iron phenotypes in a in the with of a single that the mutations. The for the mutant gene in was by of the slow growth and reductase The was to a the and of and the that by the be the with its and a gene were the of the in a This was with and exhibited slow growth and reductase of the and the also that the in for the mutant phenotypes was in or to this The mutant alleles were from and by of and analysis single changes in was from to from to mutant for a truncated protein its the was from to from to and is predicted to for a severely truncated protein The of the of the in that be or The of this mutant was in of that gene required for growth (11Strain J. Lorenz C.R. Bode J. Garland S. Smolen G.A. Ta D.T. Vickery L.E. Culotta V.C. J. Biol. Chem. 1998; 273: 31138-31144Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar). the of of in the genetic in which the mutants were the was in this and the of the was by The was and were and the the than the The the jac1 be in were by more in yeast genetic jac1 and This slow growth of the was more or in of these yeast jac1 was and We also the in used In this the jac1 and of However, these be of Jac1p from the the a of to growth In is required for growth in yeast genetic backgrounds and in In genetic backgrounds in which the jac1 null was viable, was extremely slow and mutations. the of mutants and to more with forms of we used a as is used to PubMed Scopus Google Scholar). The of the was by slow growth and cellular iron uptake and Jac1p from a the slow growth and iron uptake phenotypes of the mutant Jac1p were to the and and these were the of in the these forms of Jac1p were by the the growth and iron uptake levels from mutants and these expression of truncated Jac1p from was with the protein from the The results suggest that the domain of Jac1p is required for protein and exhibited of the gene iron reductase was repressed by iron to the The and the mutants, and were in with of iron. The were and high affinity iron uptake was by with iron iron of and mutants were to iron in the growth repressed cellular iron uptake in to a than in the mutants is a protein that with in the of In the of to these and expression of the components of the high affinity system Y. R. Dancis A. Klausner R. EMBO J. 1996; PubMed Scopus Google Scholar). We the of high affinity for the jac1 mutants was this the gene was and high affinity uptake was in double The results low levels of uptake for of the or the cellular iron uptake to jac1 was of and jac1 mutant were in of iron with as a of mitochondria were isolated and iron was by the iron of mitochondrial iron in the was of protein and for and These mitochondrial iron for the mutants are or levels of mitochondrial iron in in of iron in the growth and mutants of iron in mitochondria the in or mitochondrial iron was to or mutant the levels were and protein, These results that and to of iron to mitochondria. proteins were in the and is a mitochondrial protein D. G.J. Mol. Cell. Biol. PubMed Scopus Google Scholar), which contains a required to the of to H. J. Biol. Chem. Full Text PDF PubMed Google Scholar). protein and in the were by iron of the growth in the mutants, protein was severely that was by The was more and was in this was the iron of the mitochondria. In mitochondria isolated from the mutants in low iron was of in the mitochondria isolated from iron to iron in the was or In protein and were in mutants growth Iron accumulation within mitochondria be with of the of suggesting a toxic dehydrogenase a protein of the Fe-S and was also E. S. J. Biol. Chem. 273: Full Text Full Text PDF Scopus Google Scholar). was in the mutants and the of or to be compromised by growth in high iron Iron is in mitochondria R. J. Biol. Chem. Full Text PDF PubMed Google Scholar), and proteins are found in mitochondria. the of proteins was in the jac1 and are mitochondrial proteins that The in these proteins can be using by of its C. A.G. PubMed Scopus Google Scholar). and levels in mitochondria were in the and the iron The levels were in mitochondria with iron encoded protein was also in the and mutants This of or of in the the proteins of the are in the of cofactor this of in jac1 mutants from mitochondrial Jac1p was the of the and the was with this regulated using the for Jac1p was highly This and was from the the was Jac1p was and was from the and or of which is to this of growth was we this in the of phenotypes for the jac1 mutants were found to be to affinity iron uptake was with and were to and of In contrast with the in which protein and were in these Jac1p was protein was The is that was The protein a as for H. J. Biol. Chem. PubMed Scopus Google Scholar). to of the or to the in the Jac1p in and was as from the jac1 mutant the phenotypes from Jac1p were more than the phenotypes of the jac1 mutants, of Jac1p was from The J-proteins of and with the Hsp70, in and of precursor proteins C. B. C. E. B. W. Cell. 1994; Full Text PDF PubMed Scopus Google Scholar, B. W. J. Mol. Biol. PubMed Scopus Google Scholar). jac1 mutants were in protein we of precursor mitochondria isolated from and is a mitochondrial matrix protein involved in The precursor was in in the of with a more mature was to of the mitochondrial and this mature was from The and of the mature were in mutant mitochondria and or mutant mitochondria In a was and with the the levels of were in in the processing of Yfh1p precursor was inssq1 mutant mitochondria (8Knight S.A. Sepuri N.B. Pain D. Dancis A. J. Biol. Chem. 1998; 273: 18389-18393Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar, C. B. M. H. J. Craig Mol. Cell. Biol. 20: PubMed Scopus Google Scholar). the yeast is required for iron M. de Silva D. R. S. S. L. M. Kaplan J. Science. PubMed Scopus Google Scholar). The precursor is and the amino in by the matrix processing peptidase P. J. G. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar, Kogan M. Knight S.A. Dancis A. Pain D. Mol. PubMed Scopus Google Scholar). In ssq1 mutants, the processing is the functional of this is we that Ssq1p with Jac1p, the jac1 mutant a similar in Yfh1p Yfh1p precursor was and and mutant mitochondria. In the the precursor was to the mature and from and The intermediate by the processing was of the precursor in this partially and this was from and In the the intermediate was in the processing of the of the was as as in the ssq1 mutant and In and jac1 mutant mitochondria similar in Yfh1p The of Jac1p a mitochondrial the amino of the predicted (11Strain J. Lorenz C.R. Bode J. Garland S. Smolen G.A. Ta D.T. Vickery L.E. Culotta V.C. J. Biol. Chem. 1998; 273: 31138-31144Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar). the of a mitochondrial the Jac1p precursor protein was and in the Jac1p precursor was with the protein was to a more with mitochondria also a with The of the mature was the of a and was by the of and The mature was from that this is the Jac1p is mitochondria and to a mature by of the precursor and mature forms be with the of a mitochondrial the amino of The localization of Jac1p in was of mitochondria from the a mature Jac1p The abundance of Jac1p was in mitochondria isolated from yeast in of from to of iron regulation of protein levels In the mutants, and Jac1p was with of the the and to be null was by Jac1p and a mitochondrial protein, were in this a protein, was The within the of Jac1p was found in mitochondria in The and jac1 to analysis of these ssq1 and jac1 were the the double was and were and and were and and the double mutants In the double mutant of or the double mutants were more compromised than either of the single mutants in of and The suggest that the and for this is by Overexpression of Jac1p in Δssq1 mutants suppressed the slow growth Overexpression of Ssq1p in mutants also the effect was as to of Jac1p was of Ssq1p, and vice of Ssq1p was of Jac1p In the mutant Ssq1p was of the Jac1p and in Jac1p was of the Ssq1p jac1 mutants were isolated by to the gene of iron homeostasis. jac1 failed to cellular iron uptake in response to iron and the iron within mitochondria. The iron was with Fe-S protein The for the is that Jac1p is involved in the of or more protein H. Chem. Biol. 1999; PubMed Scopus Google Scholar). of Jac1p in to these Fe-S which in to to iron uptake to the and iron accumulation in mitochondria. The of Fe-S protein of iron to be that by transcription of (7Yamaguchi-Iwai Y. Dancis A. Klausner R.D. EMBO J. 1995; 14: 1231-1239Crossref PubMed Scopus (314) Google Scholar), is required for the induced cellular iron uptake Fe-S or with protein that contains a However, mitochondrial iron accumulation with and accumulation of mitochondrial iron be to of jac1 in is Fe-S protein with iron R.D. Cell. Full Text PDF PubMed Scopus Google Scholar), protein in yeast Jac1p to the of J-domain chaperones predicted to with Hsp70 proteins. We have now to suggest that Ssq1p is the Hsp70 for The mutant phenotypes from in either jac1 were extremely alleles of were selected in for iron (11Strain J. Lorenz C.R. Bode J. Garland S. Smolen G.A. Ta D.T. Vickery L.E. Culotta V.C. J. Biol. Chem. 1998; 273: 31138-31144Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar). The iron were similar for mutants, by of high affinity cellular iron uptake and accumulation in mitochondria. of jac1 and ssq1 (11Strain J. Lorenz C.R. Bode J. Garland S. Smolen G.A. Ta D.T. Vickery L.E. Culotta V.C. J. Biol. Chem. 1998; 273: 31138-31144Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar, B. C. H. Craig E. Proc. Natl. Acad. Sci. U. S. A. 1999; PubMed Scopus Google exhibited Fe-S protein or ssq1 (10Schilke B. Forster J. Davis J. James P. Walter W. Laloraya S. Johnson J. Miao B. Craig E. J. Cell Biol. 1996; 134: 603-613Crossref PubMed Scopus (72) Google mutant mitochondria was However, a in the processing of Yfh1p was for mutant mitochondria genetic for the interaction The double mutant was more slow than either single mutant, additive or synthetic The of Jac1p was to for the slow growth of the Δssq1 mutant, and the of Ssq1p was to for the slow growth of the Ssq1p (10Schilke B. Forster J. Davis J. James P. Walter W. Laloraya S. Johnson J. Miao B. Craig E. J. Cell Biol. 1996; 134: 603-613Crossref PubMed Scopus (72) Google and Jac1p have to mitochondria and in the same cellular as be required for to are similar proteins that domain and a domain to with proteins 1996; PubMed Scopus Google Scholar). in cellular and by or 1996; PubMed Scopus Google Scholar). of J-proteins is to of chaperone to the The also the of the Hsp70 Science. PubMed Scopus Google Scholar). the more to the to 1996; PubMed Scopus Google Scholar). However, J-proteins and with protein and chaperone 1996; PubMed Scopus Google Scholar). The the synthetic of the mutants and the are with the of and for Hsp70 and to the of the for this chaperone In of the in Fe-S proteins in the jac1 mutants, Fe-S proteins chaperone mitochondrial including Fe-S are and mitochondria as G. B. Science. 1996; 271: PubMed Scopus Google Scholar). this these Fe-S and be to chaperones the Fe-S is and or of the proteins that mediate Fe-S be the chaperone that proteins associated the of E. mediate in or of Fe-S L. D. D. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar, P. J. Johnson M. D. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar), and these chaperones for or from Vickery and Vickery L.E. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google that the protein, to be a which Fe-S with high affinity with the to and to This in is a the In the and are mitochondrial proteins that are for iron B. C. H. Craig E. Proc. Natl. Acad. Sci. U. S. A. 1999; PubMed Scopus Google Scholar). protein that be a for the Ssq1p and Jac1p chaperones is the yeast is involved in cellular and mitochondrial iron M. de Silva D. R. S. S. L. M. Kaplan J. Science. PubMed Scopus Google Scholar), the is the L. D. D. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar). and to the of these and proteins involved in Fe-S P. J. Johnson M. D. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar), are from to yeast to Mol. Cell. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar, EMBO J. PubMed Scopus Google Scholar). Ssq1p and Jac1p are to in Fe-S or L. D. D. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar, L.E. Ta D.T. Sci. PubMed Scopus Google Scholar). is that Jac1p and Ssq1p chaperones also be found in of Jac1p and Ssq1p be in of iron as R. Pain D. Dancis A. J. 1999; Full Text Full Text PDF PubMed Scopus Google and Hoffman R. Benz E. Shattil S. Furie B. Cohen H. Silberstein L. McGlave P. Hematology: Basic Principles and Practice.in: Churchill Livingstone, Philadelphia2000: Scholar, R. A. M. Mol. 1999; PubMed Scopus Google Scholar, S. G. H. E. J. R. PubMed Google Scholar).