Figure 8. Model explaining the metabolic phenotype of Cox6a2 ^−/− mice.

Loss of COX6A2 protein (ΔCOX6A2) in complex IV enhances ROS production by the respiratory chain, which activates AMPK, PGC-1α and upregulates uncoupling protein expression in skeletal muscle. This results in increased energy expenditure, non-shivering thermogenesis, as well as muscle fiber type switch and enhanced insulin sensitivity.