Mammalian Frataxin: An Essential Function for Cellular Viability through an Interaction with a Preformed ISCU/NFS1/ISD11 Iron-Sulfur Assembly Complex
In: PLoS ONE, Jg. 6 (2011), Heft 1
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Zugriff:
Background Frataxin, the mitochondrial protein deficient in Friedreich ataxia, a rare autosomal recessive neurodegenerative disorder, is thought to be involved in multiple iron-dependent mitochondrial pathways. In particular, frataxin plays an important role in the formation of iron-sulfur (Fe-S) clusters biogenesis. Methodology/Principal Findings We present data providing new insights into the interactions of mammalian frataxin with the Fe-S assembly complex by combining in vitro and in vivo approaches. Through immunoprecipitation experiments, we show that the main endogenous interactors of a recombinant mature human frataxin are ISCU, NFS1 and ISD11, the components of the core Fe-S assembly complex. Furthemore, using a heterologous expression system, we demonstrate that mammalian frataxin interacts with the preformed core complex, rather than with the individual components. The quaternary complex can be isolated in a stable form and has a molecular mass of ≈190 kDa. Finally, we demonstrate that the mature human FXN81–210 form of frataxin is the essential functional form in vivo. Conclusions/Significance Our results suggest that the interaction of frataxin with the core ISCU/NFS1/ISD11 complex most likely defines the essential function of frataxin. Our results provide new elements important for further understanding the early steps of de novo Fe-S cluster biosynthesis.
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Mammalian Frataxin: An Essential Function for Cellular Viability through an Interaction with a Preformed ISCU/NFS1/ISD11 Iron-Sulfur Assembly Complex
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Autor/in / Beteiligte Person: | Schmucker, Stéphane ; Wattenhofer-Donzé, Marie ; Puccio, Hélène ; Martelli, Alain ; Reutenauer, Laurence ; Colin, Florent ; Page, Adeline |
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Zeitschrift: | PLoS ONE, Jg. 6 (2011), Heft 1 |
Veröffentlichung: | Public Library of Science, 2011 |
Medientyp: | unknown |
ISSN: | 1932-6203 (print) |
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