A long-term goal of our laboratory is to identify strategies with which to suppress mitochondrial dysfunction. Using a genome-wide CRISPR screen we made the unexpected discovery that hypoxia or low oxygen can suppress mitochondrial dysfunction in a variety of cellular and animal models. Our initial paper reporting this discovery went on to show that low inhaled oxygen can suppress neurological disease in an accurate mouse model of mitochondrial Leigh syndrome due to mitochondrial complex I deficiency. We subsequently showed that in this same mouse model, hypoxia not only prevents the development of Leigh syndrome, but also can reverse neurological disease in the mouse model with advanced disease, and that the pathology in this disorder is most likely attributable to high, unused oxygen in the brains of these mice. More recently we have been able to show that yeast, worm, and mouse models of Friedreich’s ataxia -- due to recessive loss of frataxin -- are suppressed by low oxygen and worsened by high oxygen. In ongoing work we are deciphering the mechanism by which low oxygen alleviates pathology, and how high oxygen can exacerbate disease.