Abstract
Frataxin is a small protein involved in the rare disease Friedreich's ataxia. During the last few years, significant knowledge has been gained concerning frataxin folding, structure, dynamics, and function. In eukaryotic organisms, it is located in the mitochondrial matrix, and recently, its macromolecular context was revealed. This protein is part of a decameric supercomplex consisting of six subunits required for iron-sulfur cluster assembly, where two of them alternate in a mutually exclusive manner. Regarding Frataxin, pathogenic variants were studied, and while some exhibited reduced conformational stability, others presented an altered function. In this review, we focused on different aspects concerning the biophysics and the biochemistry of frataxin and its partners, as well as on the current knowledge regarding proteostasis and post-translational modifications. The involvement of frataxin and its partners in diseases will also be addressed, including the current therapeutic approaches. Finally, a section is dedicated to understanding the phylogenetic distribution of frataxin.