There are approximately 1500 proteins that are needed for mitochondrial 
structure and function, most of which are encoded in the nuclear genome (Calvo 
et al., 2006). Each mitochondrion has its own genome (mtDNA), which in humans 
encodes 13 polypeptides, 22 tRNAs and 2 rRNAs required for oxidative 
phosphorylation. The mitochondrial genome of humans and most vertebrates is 
approximately 16.5kbp, double-stranded, circular, with few non-coding bases. 
Thus, maintaining mtDNA stability, that is, the ability of the cell to maintain 
adequate levels of mtDNA template for oxidative phosphorylation is essential and 
can be impacted by the level of mtDNA mutation currently within the cell or 
mitochondrion, but also from errors made during normal mtDNA replication, 
defects in mitochondrial quality control mechanisms, and exacerbated by 
exposures to exogenous and/or endogenous genotoxic agents. In this review, we 
expand on the origins and consequences of mtDNA instability, the current state 
of research regarding the mechanisms by which mtDNA instability can be overcome 
by cellular and chemical interventions, and the future of research and 
treatments for mtDNA instability.