Mitochondrial DNA (mtDNA)

Mitochondrial DNA (mtDNA) is a circular, double-stranded genome of approximately 16,569 base pairs present in multiple copies per cell that encodes 13 essential subunits of the oxidative phosphorylation complexes, 22 transfer RNAs and 2 ribosomal RNAs required for their mitochondria-local translation. Unlike nuclear DNA, mtDNA is packaged in nucleoids without protective histones, is physically proximate to the electron transport chain — a major ROS source — and relies on a distinct and less-redundant set of repair enzymes, making it more susceptible to oxidative damage. Somatic mtDNA mutations and deletions accumulate with age and are elevated in post-mitotic tissues such as muscle and brain; their functional significance ranges from contributing to mitochondrial dysfunction when heteroplasmy crosses threshold levels to triggering cGAS-STING innate immune activation when cytosolic mtDNA is released during cellular stress.