Pignataro María Florencia, Noguera Martín Ezequiel, Herrera María Georgina, Roman Ernesto Andrés, Santos Javier
Departamento de Fisiología y Biología Molecular y Celular, Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Güiraldes, Autonomous City of Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas, Autonomous City of Buenos Aires, Argentina.
Biophys Rev. 2025 Apr 3;17(2):449-465. doi: 10.1007/s12551-025-01311-z. eCollection 2025 Apr.
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.
弗里德赖希共济失调蛋白是一种与罕见病弗里德赖希共济失调相关的小蛋白。在过去几年中，人们在弗里德赖希共济失调蛋白的折叠、结构、动力学和功能方面取得了重要认识。在真核生物中，它位于线粒体基质中，最近，其大分子环境也被揭示出来。该蛋白是一个十聚体超复合物的一部分，该超复合物由铁硫簇组装所需的六个亚基组成，其中两个亚基以互斥的方式交替出现。关于弗里德赖希共济失调蛋白，人们研究了其致病变体，其中一些表现出构象稳定性降低，而另一些则呈现出功能改变。在这篇综述中，我们重点关注了弗里德赖希共济失调蛋白及其伙伴的生物物理学和生物化学的不同方面，以及目前关于蛋白质稳态和翻译后修饰的知识。弗里德赖希共济失调蛋白及其伙伴在疾病中的作用也将被探讨，包括当前的治疗方法。最后，有一部分内容专门用于了解弗里德赖希共济失调蛋白的系统发育分布。
