The small (16,569 base pair) human mitochondrial genome plays a significant role 
in cell metabolism and homeostasis. Mitochondrial DNA (mtDNA) contributes to the 
generation of complexes which are essential to oxidative phosphorylation 
(OXPHOS). As such, mtDNA is directly integrated into mitochondrial biogenesis 
and signaling and regulates mitochondrial metabolism in concert with 
nuclear-encoded mitochondrial factors. Mitochondria are a highly dynamic, 
pleiomorphic network that undergoes fission and fusion events. Within this 
network, mtDNAs are packaged into structures called nucleoids which are actively 
distributed in discrete foci within the network. This sensitive organelle is 
frequently disrupted by insults such as oxidants and inflammatory cytokines, and 
undergoes genomic damage with double- and single-strand breaks that impair its 
function. Collectively, mtDNA is emerging as a highly sensitive indicator of 
cellular stress, which is directly integrated into the mitochondrial network as 
a contributor of a wide range of critical signaling pathways.