Friedreich's ataxia (FRDA) is an extremely destructive neurodegenerative mitochondrial disease with no cure to date. The disease is characterized by mutations in the FXN gene, resulting in a deficiency of functional frataxin protein. These reduced levels of frataxin protein cause multitudes of metabolic problems, including oxidative stress, disruption in iron-sulfur cluster synthesis, and iron overload in mitochondria. Recently, it has been discovered that hypoxia can rescue frataxin deficiency in various types of model organisms, including yeast, cultured human cells, nematodes, and mice. However, despite frataxin and oxygen’s integral relationship in mitochondrial function, the exact genetic pathways by which they interact remain elusive. I aim to bridge this gap by using yeast homolog and studying its oxygen dependence. YFH1 is the yeast frataxin homolog that can mimic FRDA pathology. I first created a yeast model of ∆yfh1. I am currently in the process of creating synthetic lethals and rescues of ∆yfh1 by mating it with previously identified yeast knockout strains that are known to show hypoxic resistance. After I obtain these double mutants, I plan to screen them for oxygen dependence by subjecting them under hypoxia, normoxia, and hyperoxia. Finally, I will replica plate my experiments in order to confirm the double mutants. Because ∆yfh1 is known to grow better in hypoxia, genes that create synthetic lethals in hypoxia with ∆yfh1 will most likely be the genes involved in genetic pathways of hypoxic rescue of frataxin deficiency. This will not only streamline the process of searching for the genetic basis of the disease but also serve as a platform for novel therapy to treat FRDA at its biochemical basis.