Mitochondrial DNA maintenance and expression
The mitochondrial genome is a vital component of animal metabolism, physiology, and development. C. elegans mitochondrial DNA (mtDNA) is typical of animal mitochondrial genomes in its size, 13,794 nucleotides in length, and gene content of 32 genes: 2 ribosomal RNAs, 22 transfer RNAs, and 12 protein subunits of the mitochondrial respiratory chain (MRC). Unlike nuclear DNA, mtDNA is maternally inherited and can be present at tens to tens of thousands of copies per cell. Its copy number is developmentally regulated, with mtDNA increasing about 30-fold between the L1 and the adult stages. Blocking mtDNA increase leads to larval arrest. Underlying its essential role in the biology of C. elegans, over 200 nuclear genes are needed to replicate, transcribe, and maintain the mitochondrial genome and to assemble the translation machinery required for expressing mitochondrial proteins. Disruptions in these processes have shown that the mitochondrion plays a critical role in aging, life span determination, reactive oxygen species response, the unfolded protein response, and apoptosis. Oddly, despite the essential role of mtDNA encoded genes in the cellular and organismal biology of C. elegans, mutations in mtDNA have not been reported. By contrast, over 300 lesions in human mtDNA have been described, many associated with neurological, endocrinological or muscle diseases.