Figure 8. Scheme illustrating a regulatory pathway including PGC-1α and SIRT3 governing ROS level and mitochondrial biogenesis.

PGC-1α coactivates ERRα to stimulate the expression of mSIRT3, which, in turn, increases the expression of the ROS-detoxifying enzymes GPx1 and SOD2 to suppress the ROS levels. Meanwhile, ectopic expression of SIRT3 leads to an increase of CREB phosphorylation, which subsequently stimulates the expression of PGC-1α and its target gene UCP1, finally decreasing intracellular ROS level. SIRT3 is also involved in mitochondrial biogenesis.