The genetics of mitochondrial disease

Semin Neurol. 2011 Nov;31(5):519-30. doi: 10.1055/s-0031-1299790. Epub 2012 Jan 21.


The discovery that defects in mitochondria and mitochondrial DNA could cause human disease has led to the development of a rapidly expanding group of disorders known as mitochondrial disease. Mitochondrial disease is so named because of the common feature of impaired mitochondrial function. The main function of the mitochondrion is to produce energy for the cell in the form of ATP. ATP is generated by the respiratory chain, a series of complex proteins that are located in the mitochondrial membrane, and are encoded for by both the mitochondrial and nuclear genomes. Consequently, mitochondrial disease can be caused by mutations in either mitochondrial or nuclear DNA. Given the distribution of mitochondria throughout the body, the specific properties of mitochondrial DNA, and the mitochondrion's dependence on nuclear genes for its normal function, the clinical presentation of mitochondrial disease can be highly variable. Thus, familiarity with typical clinical presentations and knowledge of the genes that contribute to mitochondrial function will aid the clinician in the recognition, diagnosis, and management of patients with this group of diverse disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DNA / metabolism
  • DNA, Mitochondrial / metabolism
  • Electron Transport / genetics*
  • Humans
  • Kearns-Sayre Syndrome / genetics
  • Leigh Disease / genetics
  • MELAS Syndrome / genetics
  • MERRF Syndrome / genetics
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Mitochondrial Diseases / genetics*
  • Mutation
  • Optic Atrophy, Hereditary, Leber / genetics


  • DNA, Mitochondrial
  • DNA