Human mitochondrial nucleases

Mitochondria are cytosolic organelles that have many essential rolesincluding ATP production via oxidative phosphorylation, apoptosis, iron-sulfur cluster biogenesis, heme and steroid synthesis, calcium homeostasis,and regulation of cellular redox state. One of the unique features of theseorganelles is the presence of an extrachromosomal mitochondrial genome (mtDNA), together with all the machinery required to replicate and tran-scribe mtDNA. The accurate maintenance of mitochondrial gene expres-sion is essential for correct organellar metabolism, and is in part dependenton the levels of mtDNA and mtRNA, which are regulated by balancingsynthesis against degradation. It is clear that although a number of mito-chondrial nucleases have been identified, not all those responsible for thedegradation of DNA or RNA have been characterized. Recent investiga-tions, however, have revealed the contribution that mutations in the genescoding for these enzymes has made to causing pathogenic mitochondrial diseases.