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A Review of Multiple Mitochondrial Dysfunction Syndromes, Syndromes Associated with Defective Fe-S Protein Maturation
Article

A Combined Spectroscopic and In Silico Approach to Evaluate the Interaction of Human Frataxin with Mitochondrial Superoxide Dismutase

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Department of Biology, University of Padova, Viale G. Colombo 3, 35131 Padova, Italy
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Department of Chemical Sciences, University of Padova, Via F. Marzolo 1, 35131 Padova, Italy
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Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3), Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Güiraldes 2160, Ciudad Universitaria, Buenos Aires C1428EGA, Argentina
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Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Güiraldes 2160, Ciudad Universitaria, Buenos Aires C1428EGA, Argentina
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Aix Marseille Universitè, CNRS, ICR, UMR 7273, case 551, Ave Escadrille Normandie Niemen, CEDEX 20, 13397 Marseille, France
*
Author to whom correspondence should be addressed.
Academic Editor: Jan Ježek
Biomedicines 2021, 9(12), 1763; https://doi.org/10.3390/biomedicines9121763
Received: 23 October 2021 / Revised: 15 November 2021 / Accepted: 22 November 2021 / Published: 25 November 2021
(This article belongs to the Special Issue Fe-S Proteins in Health and Disease)
Frataxin (FXN) is a highly conserved mitochondrial protein whose deficiency causes Friedreich’s ataxia, a neurodegenerative disease. The precise physiological function of FXN is still unclear; however, there is experimental evidence that the protein is involved in biosynthetic iron–sulfur cluster machinery, redox imbalance, and iron homeostasis. FXN is synthesized in the cytosol and imported into the mitochondria, where it is proteolytically cleaved to the mature form. Its involvement in the redox imbalance suggests that FXN could interact with mitochondrial superoxide dismutase (SOD2), a key enzyme in antioxidant cellular defense. In this work, we use site-directed spin labelling coupled to electron paramagnetic resonance spectroscopy (SDSL-EPR) and fluorescence quenching experiments to investigate the interaction between human FXN and SOD2 in vitro. Spectroscopic data are combined with rigid body protein–protein docking to assess the potential structure of the FXN-SOD2 complex, which leaves the metal binding region of FXN accessible to the solvent. We provide evidence that human FXN interacts with human SOD2 in vitro and that the complex is in fast exchange. This interaction could be relevant during the assembly of iron-sulfur (FeS) clusters and/or their incorporation in proteins when FeS clusters are potentially susceptible to attacks by reactive oxygen species. View Full-Text
Keywords: frataxin; Friedreich’s ataxia; SDSL-EPR; fluorescence; protein-protein docking; molecular dynamics frataxin; Friedreich’s ataxia; SDSL-EPR; fluorescence; protein-protein docking; molecular dynamics
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MDPI and ACS Style

Doni, D.; Meggiolaro, M.; Santos, J.; Audran, G.; Marque, S.R.A.; Costantini, P.; Bortolus, M.; Carbonera, D. A Combined Spectroscopic and In Silico Approach to Evaluate the Interaction of Human Frataxin with Mitochondrial Superoxide Dismutase. Biomedicines 2021, 9, 1763. https://doi.org/10.3390/biomedicines9121763

AMA Style

Doni D, Meggiolaro M, Santos J, Audran G, Marque SRA, Costantini P, Bortolus M, Carbonera D. A Combined Spectroscopic and In Silico Approach to Evaluate the Interaction of Human Frataxin with Mitochondrial Superoxide Dismutase. Biomedicines. 2021; 9(12):1763. https://doi.org/10.3390/biomedicines9121763

Chicago/Turabian Style

Doni, Davide, Marta Meggiolaro, Javier Santos, Gérard Audran, Sylvain R.A. Marque, Paola Costantini, Marco Bortolus, and Donatella Carbonera. 2021. "A Combined Spectroscopic and In Silico Approach to Evaluate the Interaction of Human Frataxin with Mitochondrial Superoxide Dismutase" Biomedicines 9, no. 12: 1763. https://doi.org/10.3390/biomedicines9121763

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