Mitochondrial ROS-Modulated mtDNA: A Potential Target for Cardiac Aging

Figure 4

Crucial roles of SIRT1 and SIRT3 in regulation of mitochondrial biogenesis and oxidative stress. SIRT1 is located in the nuclei and regulates mitochondrial functions by deacetylating Foxo3a and attenuating its function to reduce the expression of inflammatory proteins. SIRT1 activates PGC-1α by deacetylating the lysine residues to induce mitochondrial biogenesis. Oxidative stress inactivates SIRT3, resulting in the inactivation of SOD2 hyperacetylation and induction of mtROS. This forms a vicious cycle between mitochondrial dysfunction and mitochondrial oxidative stress. The increased ROS can be reduced by SIRT3-mediated deacetylation and activation of Foxo3a and SOD2. Deacetylated Foxo3a enhances the expression of antioxidant genes SOD2 and catalase to reduce mtROS.