Pathogenic mitochondrial DNA mutations in protein-coding genes

Muscle Nerve. 2007 Sep;36(3):279-93. doi: 10.1002/mus.20807.


More than 200 disease-related mitochondrial DNA (mtDNA) point mutations have been reported in the Mitomap ( database. These mutations can be divided into two groups: mutations affecting mitochondrial protein synthesis, including mutations in tRNA and rRNA genes; and mutations in protein-encoding genes (mRNAs). This review focuses on mutations in mitochondrial genes that encode proteins. These mutations are involved in a broad spectrum of human diseases, including a variety of multisystem disorders as well as more tissue-specific diseases such as isolated myopathy and Leber hereditary optic neuropathy (LHON). Because the mitochondrial genome contains a large number of apparently neutral polymorphisms that have little pathogenic significance, along with secondary homoplasmic mutations that do not have primary disease-causing effect, the pathogenic role of all newly discovered mutations must be rigorously established. A scoring system has been applied to evaluate the pathogenicity of the mutations in mtDNA protein-encoding genes and to review the predominant clinical features and the molecular characteristics of mutations in each mtDNA-encoded respiratory chain complex.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Carrier Proteins / metabolism
  • Cytochromes b / genetics
  • DNA, Mitochondrial / chemistry*
  • Humans
  • Leigh Disease / genetics
  • Membrane Proteins / metabolism
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Myopathies / genetics*
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Mitochondrial Proton-Translocating ATPases
  • Mutation
  • Physical Fitness


  • Carrier Proteins
  • DNA, Mitochondrial
  • Membrane Proteins
  • Mitochondrial Proteins
  • Cytochromes b
  • Adenosine Triphosphatases
  • Mitochondrial Proton-Translocating ATPases
  • oligomycin sensitivity-conferring protein