Cell-free chromatin particles released from dying cells inflict mitochondrial damage and ROS production in living cells

mtDNA damage and the resultant oxidative stress are associated with neurodegenerative diseases, ageing and cancer. However, what triggers mtDNA damage remains unclear. We have reported that cell-free chromatin particles (cfChPs) that are released from the billions of cells that die in the body every day can readily enter into healthy cells and damage their DNA. We show here that cfChPs isolated from sera of healthy individuals, or those that are released from dying cells, inflict direct physical damage mtDNA leading to marked activation of ROS. The latter could be abrogated by concurrent treatment with three different cfChPs deactivating agents. Given that 1×10 9 -1×10 12 cells die in the body every day, our findings suggest that cfChPs from dying cells are major physiological triggers for mtDNA damage and ROS production. Deactivation of cfChPs may provide a novel therapeutic approach to retard ageing and associated degenerative conditions that have been linked to oxidative stress.