Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (145)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Mühlenhoff, U.
Right arrow Articles by Lill, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mühlenhoff, U.
Right arrow Articles by Lill, R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2002, Vol. 11, No. 17 2025-2036
© 2002 Oxford University Press

The yeast frataxin homolog Yfh1p plays a specific role in the maturation of cellular Fe/S proteins

Ulrich Mühlenhoff1, Nadine Richhardt1, Michael Ristow2, Gyula Kispal3 and Roland Lill1,*

1Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Robert-Koch Str. 5, 35033 Marburg, Germany, 2Deutsches Institut für Ernährungsforschung, Arthur-Scheunert-Allee 114, 14558 Potsdam, Germany and 3Institute of Biochemistry, Medical Faculty, University of Pecs, Szigeti ut 12, 7624 Pecs, Hungary

Received April 26, 2002; Revised June 20, 2002; Accepted June 21, 2002

The mitochondrial matrix protein frataxin is depleted in patients with Friedreich's ataxia, the most common autosomal recessive ataxia. While frataxin is important for intracellular iron homeostasis, its exact cellular role is unknown. Deletion of the yeast frataxin homolog YFH1 yields mutants ({Delta}yfh1) that, depending on the genetic background, display various degrees of phenotypic defects. This renders it difficult to distinguish primary (early) from secondary (late) consequences of Yfh1p deficiency. We have constructed a yeast strain (Gal-YFH1) that carries the YFH1 gene under the control of a galactose-regulated promoter. Yfh1p-deficient Gal-YFH1 cells are far less sensitive to oxidative stress than {Delta}yfh1 mutants, maintain mitochondrial DNA, and synthesize heme at wild-type rates. Yfh1p depletion causes a strong reduction in the assembly of mitochondrial Fe/S proteins both in vivo and in detergent extracts of mitochondria. Impaired Fe/S protein biogenesis explains the respiratory deficiency of Gal-YFH1 cells. Furthermore, Yfh1p-depleted Gal-YFH1 cells show decreased maturation of cytosolic Fe/S proteins and accumulation of mitochondrial iron. This latter phenotype is common for defects in cytosolic Fe/S protein assembly. Together, our data demonstrate a specific role of frataxin in the biosynthesis of cellular Fe/S proteins and exclude most of the previously suggested functions. Friedreich's ataxia may therefore represent a disorder caused by defects in Fe/S protein maturation.

* To whom correspondence should be addressed. Tel: +49 64212866449; Fax: +49 64212866414; Email: lill{at}mailer.uni-marburg.de


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
S. Leidgens, S. De Smet, and F. Foury
Frataxin interacts with Isu1 through a conserved tryptophan in its {beta}-sheet
Hum. Mol. Genet., November 11, 2009; (2009) ddp495v2.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. L.-H. Huang, E. M. Becker, M. Whitnall, Y. S. Rahmanto, P. Ponka, and D. R. Richardson
Elucidation of the mechanism of mitochondrial iron loading in Friedreich's ataxia by analysis of a mouse mutant
PNAS, September 22, 2009; 106(38): 16381 - 16386.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Naranuntarat, L. T. Jensen, S. Pazicni, J. E. Penner-Hahn, and V. C. Culotta
The Interaction of Mitochondrial Iron with Manganese Superoxide Dismutase
J. Biol. Chem., August 21, 2009; 284(34): 22633 - 22640.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Campanella, E. Rovelli, P. Santambrogio, A. Cozzi, F. Taroni, and S. Levi
Mitochondrial ferritin limits oxidative damage regulating mitochondrial iron availability: hypothesis for a protective role in Friedreich ataxia
Hum. Mol. Genet., January 1, 2009; 18(1): 1 - 11.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. Gakh, D. Y. Smith IV, and G. Isaya
Assembly of the Iron-binding Protein Frataxin in Saccharomyces cerevisiae Responds to Dynamic Changes in Mitochondrial Iron Influx and Stress Level
J. Biol. Chem., November 14, 2008; 283(46): 31500 - 31510.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Wang and E. A. Craig
Binding of Yeast Frataxin to the Scaffold for Fe-S Cluster Biogenesis, Isu
J. Biol. Chem., May 2, 2008; 283(18): 12674 - 12679.
[Abstract] [Full Text] [PDF]

Home page
 J R Soc InterfaceHome page
P. R Kensche, V. van Noort, B. E Dutilh, and M. A Huynen
Practical and theoretical advances in predicting the function of a protein by its phylogenetic distribution
J R Soc Interface, February 6, 2008; 5(19): 151 - 170.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Amutha, D. M. Gordon, Y. Gu, E. R. Lyver, A. Dancis, and D. Pain
GTP Is Required for Iron-Sulfur Cluster Biogenesis in Mitochondria
J. Biol. Chem., January 18, 2008; 283(3): 1362 - 1371.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P. R. Anderson, K. Kirby, W. C. Orr, A. J. Hilliker, and J. P. Phillips
Hydrogen peroxide scavenging rescues frataxin deficiency in a Drosophila model of Friedreich's ataxia
PNAS, January 15, 2008; 105(2): 611 - 616.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Martelli, M. Wattenhofer-Donze, S. Schmucker, S. Bouvet, L. Reutenauer, and H. Puccio
Frataxin is essential for extramitochondrial Fe S cluster proteins in mammalian tissues
Hum. Mol. Genet., November 15, 2007; 16(22): 2651 - 2658.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
Y. Shan, E. Napoli, and G. Cortopassi
Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones
Hum. Mol. Genet., April 15, 2007; 16(8): 929 - 941.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. Pomplun, A. Voigt, T. J. Schulz, R. Thierbach, A. F. Pfeiffer, and M. Ristow
Reduced expression of mitochondrial frataxin in mice exacerbates diet-induced obesity
PNAS, April 10, 2007; 104(15): 6377 - 6381.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Ding, J. Yang, L. C. Coleman, and S. Yeung
Distinct Iron Binding Property of Two Putative Iron Donors for the Iron-Sulfur Cluster Assembly: IscA AND THE BACTERIAL FRATAXIN ORTHOLOG CyaY UNDER PHYSIOLOGICAL AND OXIDATIVE STRESS CONDITIONS
J. Biol. Chem., March 16, 2007; 282(11): 7997 - 8004.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
J. V. Llorens, J. A. Navarro, M. J. Martinez-Sebastian, M. K. Baylies, S. Schneuwly, J. A. Botella, and M. D. Molto
Causative role of oxidative stress in a Drosophila model of Friedreich ataxia
FASEB J, February 1, 2007; 21(2): 333 - 344.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
T. Gabaldon
Computational approaches for the prediction of protein function in the mitochondrion
Am J Physiol Cell Physiol, December 1, 2006; 291(6): C1121 - C1128.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. Layer, S. Ollagnier-de Choudens, Y. Sanakis, and M. Fontecave
Iron-Sulfur Cluster Biosynthesis: CHARACTERIZATION OF ESCHERICHIA COLI CYaY AS AN IRON DONOR FOR THE ASSEMBLY OF [2Fe-2S] CLUSTERS IN THE SCAFFOLD IscU
J. Biol. Chem., June 16, 2006; 281(24): 16256 - 16263.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
I. Condo, N. Ventura, F. Malisan, B. Tomassini, and R. Testi
A Pool of Extramitochondrial Frataxin That Promotes Cell Survival
J. Biol. Chem., June 16, 2006; 281(24): 16750 - 16756.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
O. Gakh, S. Park, G. Liu, L. Macomber, J. A. Imlay, G. C. Ferreira, and G. Isaya
Mitochondrial iron detoxification is a primary function of frataxin that limits oxidative damage and preserves cell longevity
Hum. Mol. Genet., February 1, 2006; 15(3): 467 - 479.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. J. Schulz, R. Thierbach, A. Voigt, G. Drewes, B. Mietzner, P. Steinberg, A. F. H. Pfeiffer, and M. Ristow
Induction of Oxidative Metabolism by Mitochondrial Frataxin Inhibits Cancer Growth: OTTO WARBURG REVISITED
J. Biol. Chem., January 13, 2006; 281(2): 977 - 981.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. Balk, D. J. Aguilar Netz, K. Tepper, A. J. Pierik, and R. Lill
The Essential WD40 Protein Cia1 Is Involved in a Late Step of Cytosolic and Nuclear Iron-Sulfur Protein Assembly
Mol. Cell. Biol., December 15, 2005; 25(24): 10833 - 10841.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
R. A. Schoenfeld, E. Napoli, A. Wong, S. Zhan, L. Reutenauer, D. Morin, A. R. Buckpitt, F. Taroni, B. Lonnerdal, M. Ristow, et al.
Frataxin deficiency alters heme pathway transcripts and decreases mitochondrial heme metabolites in mammalian cells
Hum. Mol. Genet., December 15, 2005; 14(24): 3787 - 3799.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
R. Thierbach, T. J. Schulz, F. Isken, A. Voigt, B. Mietzner, G. Drewes, J.-C. von Kleist-Retzow, R. J. Wiesner, M. A. Magnuson, H. Puccio, et al.
Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span and tumor growth in mice
Hum. Mol. Genet., December 15, 2005; 14(24): 3857 - 3864.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
D. S. Kalinowski and D. R. Richardson
The Evolution of Iron Chelators for the Treatment of Iron Overload Disease and Cancer
Pharmacol. Rev., December 1, 2005; 57(4): 547 - 583.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
P. R. Anderson, K. Kirby, A. J. Hilliker, and J. P. Phillips
RNAi-mediated suppression of the mitochondrial iron chaperone, frataxin, in Drosophila
Hum. Mol. Genet., November 15, 2005; 14(22): 3397 - 3405.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
F. Acquaviva, I. De Biase, L. Nezi, G. Ruggiero, F. Tatangelo, C. Pisano, A. Monticelli, C. Garbi, A. M. Acquaviva, and S. Cocozza
Extra-mitochondrial localisation of frataxin and its association with IscU1 during enterocyte-like differentiation of the human colon adenocarcinoma cell line Caco-2
J. Cell Sci., September 1, 2005; 118(17): 3917 - 3924.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
P. Gonzalez-Cabo, R. P. Vazquez-Manrique, M. A. Garcia-Gimeno, P. Sanz, and F. Palau
Frataxin interacts functionally with mitochondrial electron transport chain proteins
Hum. Mol. Genet., August 1, 2005; 14(15): 2091 - 2098.
[Abstract] [Full Text] [PDF]

Home page
 Plant Physiol.Home page
S. E. Abdel-Ghany, H. Ye, G. F. Garifullina, L. Zhang, E. A.H. Pilon-Smits, and M. Pilon
Iron-Sulfur Cluster Biogenesis in Chloroplasts. Involvement of the Scaffold Protein CpIscA
Plant Physiology, May 1, 2005; 138(1): 161 - 172.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Hausmann, D. J. Aguilar Netz, J. Balk, A. J. Pierik, U. Muhlenhoff, and R. Lill
The eukaryotic P loop NTPase Nbp35: An essential component of the cytosolic and nuclear iron-sulfur protein assembly machinery
PNAS, March 1, 2005; 102(9): 3266 - 3271.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
I. Napier, P. Ponka, and D. R. Richardson
Iron trafficking in the mitochondrion: novel pathways revealed by disease
Blood, March 1, 2005; 105(5): 1867 - 1874.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
H. Seznec, D. Simon, C. Bouton, L. Reutenauer, A. Hertzog, P. Golik, V. Procaccio, M. Patel, J.-C. Drapier, M. Koenig, et al.
Friedreich ataxia: the oxidative stress paradox
Hum. Mol. Genet., February 15, 2005; 14(4): 463 - 474.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
O. Stehling, H.-P. Elsasser, B. Bruckel, U. Muhlenhoff, and R. Lill
Iron-sulfur protein maturation in human cells: evidence for a function of frataxin
Hum. Mol. Genet., December 1, 2004; 13(23): 3007 - 3015.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
E. Skovran, C. T. Lauhon, and D. M. Downs
Lack of YggX Results in Chronic Oxidative Stress and Uncovers Subtle Defects in Fe-S Cluster Metabolism in Salmonella enterica
J. Bacteriol., November 15, 2004; 186(22): 7626 - 7634.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
C. M. Everett and N. W. Wood
Trinucleotide repeats and neurodegenerative disease
Brain, November 1, 2004; 127(11): 2385 - 2405.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
S. Goffart, J.-C. von Kleist-Retzow, and R. J. Wiesner
Regulation of mitochondrial proliferation in the heart: power-plant failure contributes to cardiac failure in hypertrophy
Cardiovasc Res, November 1, 2004; 64(2): 198 - 207.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Campanella, G. Isaya, H. A. O'Neill, P. Santambrogio, A. Cozzi, P. Arosio, and S. Levi
The expression of human mitochondrial ferritin rescues respiratory function in frataxin-deficient yeast
Hum. Mol. Genet., October 1, 2004; 13(19): 2279 - 2288.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Li and J. Kaplan
A Mitochondrial-Vacuolar Signaling Pathway in Yeast That Affects Iron and Copper Metabolism
J. Biol. Chem., August 6, 2004; 279(32): 33653 - 33661.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
A.-L. Bulteau, H. A. O'Neill, M. C. Kennedy, M. Ikeda-Saito, G. Isaya, and L. I. Szweda
Frataxin Acts as an Iron Chaperone Protein to Modulate Mitochondrial Aconitase Activity
Science, July 9, 2004; 305(5681): 242 - 245.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Lange, U. Muhlenhoff, M. Denzel, G. Kispal, and R. Lill
The Heme Synthesis Defect of Mutants Impaired in Mitochondrial Iron-Sulfur Protein Biogenesis Is Caused by Reversible Inhibition of Ferrochelatase
J. Biol. Chem., July 9, 2004; 279(28): 29101 - 29108.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. S. Chen, R. J. Crisp, M. Valachovic, M. Bard, D. R. Winge, and J. Kaplan
Transcription of the Yeast Iron Regulon Does Not Respond Directly to Iron but Rather to Iron-Sulfur Cluster Biosynthesis
J. Biol. Chem., July 9, 2004; 279(28): 29513 - 29518.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Yoon and J. A. Cowan
Frataxin-mediated Iron Delivery to Ferrochelatase in the Final Step of Heme Biosynthesis
J. Biol. Chem., June 18, 2004; 279(25): 25943 - 25946.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. Gerber, K. Neumann, C. Prohl, U. Muhlenhoff, and R. Lill
The Yeast Scaffold Proteins Isu1p and Isu2p Are Required inside Mitochondria for Maturation of Cytosolic Fe/S Proteins
Mol. Cell. Biol., June 1, 2004; 24(11): 4848 - 4857.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
H. Seznec, D. Simon, L. Monassier, P. Criqui-Filipe, A. Gansmuller, P. Rustin, M. Koenig, and H. Puccio
Idebenone delays the onset of cardiac functional alteration without correction of Fe-S enzymes deficit in a mouse model for Friedreich ataxia
Hum. Mol. Genet., May 15, 2004; 13(10): 1017 - 1024.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. A. Cobine, L. D. Ojeda, K. M. Rigby, and D. R. Winge
Yeast Contain a Non-proteinaceous Pool of Copper in the Mitochondrial Matrix
J. Biol. Chem., April 2, 2004; 279(14): 14447 - 14455.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
D. Simon, H. Seznec, A. Gansmuller, N. Carelle, P. Weber, D. Metzger, P. Rustin, M. Koenig, and H. Puccio
Friedreich Ataxia Mouse Models with Progressive Cerebellar and Sensory Ataxia Reveal Autophagic Neurodegeneration in Dorsal Root Ganglia
J. Neurosci., February 25, 2004; 24(8): 1987 - 1995.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
P. Rustin, D. Bonnet, A. Rotig, A. Munnich, D. Sidi, C. Mariotti, F. Taroni, S. Di Donato, A. Filla, and A. J. Moss
Idebenone treatment in Friedreich patients: One-year-long randomized placebo-controlled trial
Neurology, February 10, 2004; 62(3): 524 - 525.
[Full Text] [PDF]

Home page
 Hum Mol GenetHome page
G. Karthikeyan, J. H. Santos, M. A. Graziewicz, W. C. Copeland, G. Isaya, B. V. Houten, and M. A. Resnick
Reduction in frataxin causes progressive accumulation of mitochondrial damage
Hum. Mol. Genet., December 15, 2003; 12(24): 3331 - 3342.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. J. Crisp, A. Pollington, C. Galea, S. Jaron, Y. Yamaguchi-Iwai, and J. Kaplan
Inhibition of Heme Biosynthesis Prevents Transcription of Iron Uptake Genes in Yeast
J. Biol. Chem., November 14, 2003; 278(46): 45499 - 45506.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
U. Muhlenhoff, J. A. Stadler, N. Richhardt, A. Seubert, T. Eickhorst, R. J. Schweyen, R. Lill, and G. Wiesenberger
A Specific Role of the Yeast Mitochondrial Carriers Mrs3/4p in Mitochondrial Iron Acquisition under Iron-limiting Conditions
J. Biol. Chem., October 17, 2003; 278(42): 40612 - 40620.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Park, O. Gakh, H. A. O'Neill, A. Mangravita, H. Nichol, G. C. Ferreira, and G. Isaya
Yeast Frataxin Sequentially Chaperones and Stores Iron by Coupling Protein Assembly with Iron Oxidation
J. Biol. Chem., August 15, 2003; 278(33): 31340 - 31351.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
G. Tan, E. Napoli, F. Taroni, and G. Cortopassi
Decreased expression of genes involved in sulfur amino acid metabolism in frataxin-deficient cells
Hum. Mol. Genet., July 15, 2003; 12(14): 1699 - 1711.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
E. Lesuisse, R. Santos, B. F. Matzanke, S. A. B. Knight, J.-M. Camadro, and A. Dancis
Iron use for haeme synthesis is under control of the yeast frataxin homologue (Yfh1)
Hum. Mol. Genet., April 15, 2003; 12(8): 879 - 889.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
O. S. Chen, S. Hemenway, and J. Kaplan
Inhibition of Fe-S cluster biosynthesis decreases mitochondrial iron export: Evidence that Yfh1p affects Fe-S cluster synthesis
PNAS, September 17, 2002; 99(19): 12321 - 12326.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.