Investigating the effects of frataxin deficiency on the human proteome

This proposal seeks to identify the proteins that are affected by frataxin loss. Frataxin contributes to the assembly of iron-sulfur clusters, which are fundamental molecular ensembles necessary for all domains of life. Proteins containing iron-sulfur clusters, iron-sulfur proteins, are important for cellular energy production, cell division and the maintenance of general cellular health. To better understand the molecular mechanism behind FA pathogenesis, Ms Xiong will study the consequences of frataxin deficiency in cells. To do so, she will use a human cell line where the FXN gene is deleted and a new technique that allows for the identification of those iron-sulfur proteins affected by the loss of frataxin. The goal is to pinpoint the group of proteins that lose their iron-sulfur clusters when frataxin is deficient. The activity of these impaired iron-sulfur proteins will then be further analyzed in FA patient cells to confirm their relevance to the molecular mechanism of FA pathogenesis. The identified iron-sulfur proteins represent new potential therapeutic targets for FA.