Aging: A mitochondrial DNA perspective, critical analysis and an update

Figure 1 “Vicious cycle” of reactive oxygen species production, mitochondrial DNA damage, mitochondrial DNA mutagenesis and further reactive oxygen species production. The cycle implies an exponential growth of reactive oxygen species (ROS) production and mitochondrial DNA (mtDNA) mutagenesis.

Figure 2 The map of human mitochondrial DNA. OH and OL: Origins of heavy and light strand replication, respectively; ND1-ND6: Subunits of NADH dehydrogenase (ETC complex I) subunits 1 through 6; COX1-COX3: Subunits of cytochrome oxidase subunits 1 through 3 (ETC complex IV); ATP6 and ATP8: Subunits 6 and 8 of mitochondrial ATPase (complex V); Cyt b: Cytochrome b (complex III); ETC: Electron transport chain.

Figure 3 Consequences of unrepaired DNA damage in the nucleus and in the mitochondria. Oxidative damage induces lesions in both nDNA (left) and mtDNA (right). Both nuclei and mitochondria possess DNA repair systems to deal with these lesions. However, cellular consequences of unrepaired damage to nDNA and mtDNA are different. While persistent damage in nDNA results in the activation of cell cycle checkpoints, growth arrest, senescence and death. In contrast, mtDNA molecules with unrepairable damage are simply degraded and new molecules are synthesized using intact molecules as templates. This figure uses Servier elements available under Creative Commons license (155).