Nevertheless, isoform switches can also occur in other normoxic systems, as exemplified by our previous observations in two rodent models; heat-acclimation-mediated cardioprotection in a rat model by mitochondrial metabolic remodeling included the upregulation of COX4-2 via HIF-1α in the heart, and additionally, we detected the upregulation of COX4-2 in brain tissue in a mouse model of prion disease [23,24]. This evidence concerns the gene COX4I2 and prion disease.