Mitochondrial disease: mutations and mechanisms

Neurochem Res. 2004 Mar;29(3):589-600. doi: 10.1023/b:nere.0000014829.42364.dd.


The mitochondrial diseases encompass a diverse group of disorders that can exhibit various combinations of clinical features. Defects in mitochondrial DNA (mtDNA) have been associated with these diseases, and studies have been able to assign biochemical defects. Deficiencies in mitochondrial oxidative phosphorylation appear to be the main pathogenic factors, although recent studies suggest that other mechanisms are involved. Reactive oxygen species (ROS) generation has been implicated in a wide variety of neurodegenerative diseases, and mitochondrial ROS generation may be an important factor in mitochondrial disease pathogenesis. Altered apoptotic signaling as a consequence of defective mitochondrial function has also been observed in both in vitro and in vivo disease models. Our current understanding of the contribution of these various mechanisms to mitochondrial disease pathophysiology will be discussed.

Publication types

  • Review

MeSH terms

  • DNA, Mitochondrial / genetics*
  • Humans
  • MELAS Syndrome / genetics
  • Mitochondria / genetics
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Myopathies / genetics
  • Mutation / genetics*
  • Oxidative Phosphorylation
  • Oxidative Stress / physiology


  • DNA, Mitochondrial