Clinical syndromes associated with mtDNA mutations: where we stand after 30 years

Essays Biochem. 2018 Jul 20;62(3):235-254. doi: 10.1042/EBC20170097. Print 2018 Jul 20.


The landmark year 1988 can be considered as the birthdate of mitochondrial medicine, when the first pathogenic mutations affecting mtDNA were associated with human diseases. Three decades later, the field still expands and we are not 'scraping the bottom of the barrel' yet. Despite the tremendous progress in terms of molecular characterization and genotype/phenotype correlations, for the vast majority of cases we still lack a deep understanding of the pathogenesis, good models to study, and effective therapeutic options. However, recent technological advances including somatic cell reprogramming to induced pluripotent stem cells (iPSCs), organoid technology, and tailored endonucleases provide unprecedented opportunities to fill these gaps, casting hope to soon cure the major primary mitochondrial phenotypes reviewed here. This group of rare diseases represents a key model for tackling the pathogenic mechanisms involving mitochondrial biology relevant to much more common disorders that affect our currently ageing population, such as diabetes and metabolic syndrome, neurodegenerative and inflammatory disorders, and cancer.

Keywords: Chronic Progressive External Ophthalmoplegia; Kearn-Sayre Syndrome; LHON; MELAS; MERRF; mitochondrial DNA mutations.

Publication types

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

MeSH terms

  • DNA, Mitochondrial / genetics*
  • Gene Deletion
  • Genetic Predisposition to Disease*
  • Genomic Imprinting
  • Humans
  • Mutation, Missense*
  • Point Mutation*
  • Rare Diseases / genetics*
  • Syndrome


  • DNA, Mitochondrial