Figure 4.

The influence of mtDNA damage on VSMCs and targeted therapies. mtDNA encodes core subunits of respiratory chain complexes I, III and IV and ATP synthase. Pathogenic mutation and aberrant methylation of mtDNA affect oxidative respiratory function. Reduced ATP and increased mtROS drive the senescence of VSMC and phenotype transition from contractile to non-contractile (synthetic). Overexpression of Twinkle increases the mtDNA copy number to shift the heterogeneity level of mutation. Administration of the SOD2 activator and antioxidants can counteract excess mtROS and restore mitochondrial homeostasis. SOD2, superoxide dismutase 2. Part of the elements in this figure are using resources from Servier Medical Art under a Creative Commons Attribution license.