Send to

Choose Destination
Hum Mutat. 2019 May 10. doi: 10.1002/humu.23789. [Epub ahead of print]

Characterization of human frataxin missense variants in cancer tissues.

Author information

Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Sapienza University of Rome, Rome, Italy.
IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
European Brain Research Institute-Fondazione Rita Levi Montalcini, Rome, Italy.
ENEA CR Frascati, Diagnostics and Metrology Laboratory, FSN-TECFIS-DIM, Frascati, Italy.
Istituto di Biologia e Patologia Molecolari del CNR, Sapienza Università di Roma, Rome, Italy.
Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy.
CNR, Institute of Translational Pharmacology, Rome, Italy.
Department of Physics, INFN, University of Rome Tor Vergata, Rome, Italy.
The Wohl Institute, King's College London, London, UK.
Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, Bologna, Italy.


Human frataxin is an iron-binding protein involved in the mitochondrial iron-sulfur (Fe-S) clusters assembly, a process fundamental for the functional activity of mitochondrial proteins. Decreased level of frataxin expression is associated with the neurodegenerative disease Friedreich ataxia. Defective function of frataxin may cause defects in mitochondria, leading to increased tumorigenesis. Tumor-initiating cells show higher iron uptake, a decrease in iron storage and a reduced Fe-S clusters synthesis and utilization. In this study, we selected, from COSMIC database, the somatic human frataxin missense variants found in cancer tissues p.D104G, p.A107V, p.F109L, p.Y123S, p.S161I, p.W173C, p.S181F, and p.S202F to analyze the effect of the single amino acid substitutions on frataxin structure, function, and stability. The spectral properties, the thermodynamic and the kinetic stability, as well as the molecular dynamics of the frataxin missense variants found in cancer tissues point to local changes confined to the environment of the mutated residues. The global fold of the variants is not altered by the amino acid substitutions; however, some of the variants show a decreased stability and a decreased functional activity in comparison with that of the wild-type protein.


cancer tissues; human frataxin; missense variants; protein folding; protein stability; protein variants; single amino acid substitution; somatic mutations


Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center