Increased TFAM binding to mtDNA damage hot spots is associated with mtDNA loss in aged rat heart

Chimienti G, Picca A, Sirago G, Fracasso F, Calvani R, Bernabei R, Russo F, Carter CS, Leeuwenburgh C, Pesce V, Marzetti E, Lezza AMS

https://www.sciencedirect.com/science/article/pii/S0891584918311614

• In aged rat hearts (27 months), the authors observe 25% decrease in mtDNA content, an anti-correlated 29% increase in the 4.8 kb mtDNA deletion relative content, and 38% decrease in TFAM levels.
• The TFAM-binding activity to specific mtDNA regions increased at the mtDNA replication origins, D-loop and Ori-L
• A marked increase in the relative content of mtDNA strand damage was found in the D-loop and Ori-L in aged animals, suggesting the existence of mutational hotspots in these regions