mitochondrial disease

Last reviewed 09/2021

The process of oxidative phosphorylation occurs in the mitochondrion. The mitochondrial proteins necessary for oxidative phosphorylation are coded both by nuclear DNA and by mitochondrial DNA. Protein and tRNA genes coded by mitochondrial DNA are more prone to mutation than nuclear genes.

Syndromes caused by point mutations in mitochondrial DNA are maternally inherited because only 0.1% of mitochondrial DNA is contributed by the sperm. Examples include:

  • myoclonic epilepsy and ragged-end fibre disease (MERRF)
  • mitochondrial encephalomyopathy, lactic acidosis and stroke-like symptoms (MELAS)
  • Leber's hereditary optic neuropathy (LHON)
  • neurogenic muscle weakness, ataxia and retinitis pigmentosum (NARP)
  • Leigh disease

Syndromes caused by insertions or deletions in mitochondrial DNA are usually sporadic. Examples include:

  • Kearns-Sayre syndrome (KSS)
  • Pearson's marrow/pancreas syndrome
  • chronic external ophthalmoplegia (CEO)

Antiviral nucleoside analogues, e.g. zidovudine, are toxic to mitochondria and have adverse effects similar to the mitochondrial diseases listed above.