ABSTRACT
Mitochondrial DNA (mtDNA) is vital for cell survival and its maintenance is ensured by multiple cellular processes, not always directly and easily connected with mtDNA function. These include replication, transcription, nucleotide biosynthesis as well as mitochondrial dynamics and others. Dysfunction of any of them can lead to mtDNA instability presenting as reduction in copy number (depletion), multiple large-scale mtDNA deletions and a higher point mutation rate. It causes oxidative phosphorylation system defect and mitochondrial disease. mtDNA depletion commonly leads to depletion syndromes manifesting usually as early onset, severe encephalopathies frequently with liver involvement while multiple mtDNA deletions are responsible for progressive external ophthalmoplegia. All the proteins involved in mtDNA stability are nuclear therefore the diseases resulting from their dysfunction show Mendelian inheritance. Sporadic single large-scale mtDNA deletions are a frequent cause of human disease as well. Mitochondrial deletions also appear with age and are found in brains of patients with neurodegenerative diseases, although their role in ageing is not clear.
The mechanism of mtDNA deletion formation is still not fully understood. It seems that double strand brake repair may be involved. The behavior of large-scale mtDNA deletions in the mitochondrion, cell, tissue and organism will be discussed, as well the influence of antiviral drugs on mtDNA stability.
