Similar findings of hyperoxia are evident in mitochondrial disease patients that exhibit elevated venous oxygen levels due to impaired tissue oxygen extraction.6 Notably, we have shown that chronic exposure to inhaled hypoxia (equivalent to an altitude of 4,500 m) normalizes this tissue hyperoxia and dramatically extends the lifespan of Ndufs4 KO mice.3,5 Remarkably, this intervention can even reverse neurological lesions at the late stages of disease.4 Here, NDUFS4 is linked to mitochondrial disease.