Mechanisms of Mitochondrial DNA Deletion Formation

Trends Genet. 2019 Mar;35(3):235-244. doi: 10.1016/j.tig.2019.01.001. Epub 2019 Jan 25.


Mitochondrial DNA (mtDNA) encodes a subset of genes which are essential for oxidative phosphorylation. Deletions in the mtDNA can ablate a number of these genes and result in mitochondrial dysfunction, which is associated with bona fide mitochondrial disorders. Although mtDNA deletions are thought to occur as a result of replication errors or following double-strand breaks, the exact mechanism(s) behind deletion formation have yet to be determined. In this review we discuss the current knowledge about the fate of mtDNA following double-strand breaks, including the molecular players which mediate the degradation of linear mtDNA fragments and possible mechanisms of recircularization. We propose that mtDNA deletions formed from replication errors versus following double-strand breaks can be mediated by separate pathways.

Keywords: double-strand breaks; mitochondrial DNA; mitochondrial DNA deletions; replication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DNA Breaks, Double-Stranded
  • DNA Damage / genetics
  • DNA Replication / genetics*
  • DNA, Mitochondrial / genetics*
  • Humans
  • Mitochondria / genetics*
  • Sequence Deletion / genetics*
  • Signal Transduction / genetics


  • DNA, Mitochondrial