Causes and Consequences of Perturbations of the Mitochondrial Genome
Mitochondria are essential subcellular organelles, generating >90% of the cellular ATP needed to meet the functional needs of the organism and carrying out a multitude of other essential functions. Mitochondria harbor an essential, high copy number, small (16,569 base pair in humans), circular DNA genome required for well-coupled electron transport and oxidative phosphorylation. Damage to this genome or alterations in the number of genomes present in each cell can result from environmental exposures, heritable mutations, or endogenous factors. mtDNA damage, mutations, and depletion can compromise cellular respiration and give rise to mitochondrial toxicity and mitochondrial disease. In this chapter, we review the structure and composition of the mitochondrial genome, the processes that maintain mtDNA integrity, function, and stability, as well as exposure-related mtDNA toxicity.
