Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin

Science

Volumn 276, Issue 5319, 1997, Pages 1709-1712

  Babcock, Michael ^a   De Silva, Deepika ^a   Oaks, Robert ^a   Davis Kaplan, Sandra ^a   Jiralerspong, Sarn ^b   Montermini, Laura ^b   Pandolfo, Massimo ^c,d   Kaplan, Jerry ^a  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^b Ctr de Rech Louis Charles Simard   (Canada)

^c UNIVERSITÉ DE MONTRÉAL   (Canada)

^d MCGILL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

FRATAXIN; UNCLASSIFIED DRUG;

ARTICLE; CARDIOMYOPATHY; CELL DAMAGE; FRIEDREICH ATAXIA; IRON METABOLISM; MOLECULAR CLONING; NERVE DEGENERATION; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PRIORITY JOURNAL; RNA ANALYSIS; SACCHAROMYCES CEREVISIAE; SEQUENCE ANALYSIS; SOUTHERN BLOTTING;

BIOLOGICAL TRANSPORT; CARRIER PROTEINS; CELL MEMBRANE; CERULOPLASMIN; CYTOSOL; FRIEDREICH ATAXIA; FUNGAL PROTEINS; GENES, FUNGAL; GENETIC COMPLEMENTATION TEST; HOMEOSTASIS; HUMANS; IRON; IRON-BINDING PROTEINS; MEMBRANE TRANSPORT PROTEINS; MITOCHONDRIA; OXIDATIVE STRESS; OXIDOREDUCTASES; PHOSPHOTRANSFERASES (ALCOHOL GROUP ACCEPTOR); RECOMBINANT FUSION PROTEINS; SACCHAROMYCES CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEINS; TRANSFORMATION, GENETIC;

ATAXIA; SACCHAROMYCES CEREVISIAE;

EID: 0030846021     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.276.5319.1709     Document Type: Article

References (36)

1. G. Geoffroy et al., Can. J. Neurol. Sci. 3, 279 (1976); A. E. Harding, Brain 104, 589 (1981).
2. G. Geoffroy et al., Can. J. Neurol. Sci. 3, 279 (1976); A. E. Harding, Brain 104, 589 (1981).
3. A. E. Harding and R. L. Hewer, Q. J. Med. 208, 489 (1983).
4. G. Finocchiaro et al., Neurology 38, 1292 (1988).
5. V. Campuzano et al., Science 271, 1423 (1996).
6. M. Cossée et al., Nature Genet. 15, 337 (1997).
7. S. Jiralerspong et al., Neurobiol. Dis., in press.
8. J. Carvajal et al., Nature Genet. 14, 157 (1996).
9. Mouse and rat homologs were also found among sequences in the expressed sequence tag (EST) database.
10. Cells (DY150), mutagenized with ethylmethane sulfonate were subjected to a streptonigrin enrichment screen followed by replica plating on low-iron [BPS(5)] and high-iron [yeast extract, peptone, and dextrose (YPD)] plates as described by C. C. Askwith et al. [Cell 76, 403 (1994)]. Low-iron medium was generated by using the iron chelator bathophenanthrolinedisulfonate (BPS). Numbers in parenthesis indicate exogenous iron added back in micromolar; for example, BPS (5) contains 5 μM iron. The bm-8 mutant grew well on YPD but exhibited a marked growth defect on iron-restricted plates.
11. The mutant bm-8 was transformed with a multicopy yeast genomic library, and the plasmid pTF63/p24 was recovered by its ability to partially restore growth of bm-8 on low-iron medium. The complementing region was narrowed by subcloning to a 1.1-kb Hind III fragment. M13 forward and reverse primers were used to sequence into the insert. The region was located on chromosome IV and shown to contain the entire open reading frame for YDL120w.
12. The complementing Hind III fragment was cloned into the centromeric vector M1188 YCP-URA pRS305, and the resulting construct was shown not to complement bm-8 on low-iron medium. The Hind III fragment was also cloned into the yeast integrative plasmid YIP-LEU2 M1091 .This construct was transformed into bm-8, and recombinants were selected on plates of complete minimal medium without leucine. The integration of LEU2 next to YFH1 was confirmed by Southern blot analysis. Recombinants were then mated to wild-type strain DY1457 and the diploids sporulated. Tetrad analysis revealed that the LEU2 marker segregated independently of the bm-8 phenotype of poor growth on low-iron medium.
13. - medium. Recombinants were verified by Southern blot analysis.
14. M. Babcock et al., data not shown.
15. K. Nakai, Bull. Inst. Chem. Res. Kyoto Univ. 69, 269 (1991).
16. A YFH1 PCR product was generated with the added restriction sites Xba I and Cla I. The forward primer was 5′-GCTCTAGAGTGTAGCAATGATTAAGC-3′, and the reverse primer was 5′-CCATCGATTTGGCTTTTAGAAATGGC-3′. The PCR product, digested with Xba I and Cla I, was cloned into the vector pGFP-C-FUS [R. K. Niedenthal et al., Yeast 12, 773 (1996)]. The resulting Yfh1p-GFP construct was transformed into yfh1::HIS3. The construct was able to complement the growth defect on YPD.
17. R. Stearman, D. S. Yuan, Y. Yamaguchi-Iwai, R. D. Klausner, A. Dancis, Science 271, 1552 (1996).
18. Y. Yamaguchi-Iwai et al., EMBO J. 14, 1231 (1995).
19. L. Schols et al., Eur. J. Neurol. 3, 55 (1996).
20. E. Bonfoco et al., Proc. Natl. Acad. Sci. U.S.A. 92, 7162 (1995).
21. J. P. Blass et al., N. Engl. J. Med. 295, 62 (1976); U. J. Dijkstra et al., Ann. Neurol. 13, 325 (1983); D. A. Stumpf et al., Neurology 32, 221 (1982). Several abnormalities were reported and thought to be the primary defect in FRDA. These include lipoamide dehydrogenase deficiency, pyruvate carboxylase deficiency, and mitochondrial malic enzyme deficiency. Subsequent studies did not confirm that any of these abnormalities could be the primary defect in FRDA.
22. J. P. Blass et al., N. Engl. J. Med. 295, 62 (1976); U. J. Dijkstra et al., Ann. Neurol. 13, 325 (1983); D. A. Stumpf et al., Neurology 32, 221 (1982). Several abnormalities were reported and thought to be the primary defect in FRDA. These include lipoamide dehydrogenase deficiency, pyruvate carboxylase deficiency, and mitochondrial malic enzyme deficiency. Subsequent studies did not confirm that any of these abnormalities could be the primary defect in FRDA.
23. J. P. Blass et al., N. Engl. J. Med. 295, 62 (1976); U. J. Dijkstra et al., Ann. Neurol. 13, 325 (1983); D. A. Stumpf et al., Neurology 32, 221 (1982). Several abnormalities were reported and thought to be the primary defect in FRDA. These include lipoamide dehydrogenase deficiency, pyruvate carboxylase deficiency, and mitochondrial malic enzyme deficiency. Subsequent studies did not confirm that any of these abnormalities could be the primary defect in FRDA.
24. R. O. Morgan et al., Can. J. Neurol. Sci. 6, 227 (1979).
25. S. Chamberlain and P. D. Lewis, J. Neurol. Neurosurg. Psychiatry 45, 1136 (1982).
26. J. B. Lamarche et al., in Handbook of Cerebellar Diseases, R. Lechtenberg, Ed. (Dekker, New York, 1993), pp. 453-457. Stainable iron was identified in cardiomyocytes from all 15 FRDA patients that were examined and none from 10 controls. No iron deposits were present in the liver, in endocrine tissues, or in the reticuloendothelial system of FRDA patients.
27. G. Barbeau, Can. J. Neurol. Sci. 7, 455 (1980).
28. A. E. Harding, Adv. Neurol. 61, 1 (1993).
29. M. Ben Hamida et al., Neurology 34, 2179 (1993).
30. S. M. Thomas et al., Biochim. Biophys. Acta 1002, 189 (1989).
31. A. Filla et al., Am. J. Hum. Genet. 59, 554 (1996); A. Dürr et al., N. Eng. J. Med. 335, 1169 (1996); L. Montermini et al., Ann. Neurol. 41, 675 (1997).
32. A. Filla et al., Am. J. Hum. Genet. 59, 554 (1996); A. Dürr et al., N. Eng. J. Med. 335, 1169 (1996); L. Montermini et al., Ann. Neurol. 41, 675 (1997).
33. A. Filla et al., Am. J. Hum. Genet. 59, 554 (1996); A. Dürr et al., N. Eng. J. Med. 335, 1169 (1996); L. Montermini et al., Ann. Neurol. 41, 675 (1997).
34. C. C. Askwith and J. Kaplan, J. Biol. Chem. 272, 401 (1997).
35. B. S. Glick and L. A. Pons, Methods Enzymol. 260, 213 (1995).
36. Supported by grants from NIH (DK49219 and DK30534 to J.K., NS34192 to M.P.), by the Muscular Dystrophy Association (M.P.), and by the Fondation Notre Dame (M.P.). D.S. was supported by a NIH postdoctoral Hematology training grant (T32DK07115), and L.M. was supported by a Medical Research Council of Canada postdoctoral fellowship.