A Brief History of Mitochondrial Pathologies

Int J Mol Sci. 2019 Nov 12;20(22):5643. doi: 10.3390/ijms20225643.


The history of "mitochondrial pathologies", namely genetic pathologies affecting mitochondrial metabolism because of mutations in nuclear DNA-encoded genes for proteins active inside mitochondria or mutations in mitochondrial DNA-encoded genes, began in 1988. In that year, two different groups of researchers discovered, respectively, large-scale single deletions of mitochondrial DNA (mtDNA) in muscle biopsies from patients with "mitochondrial myopathies" and a point mutation in the mtDNA gene for subunit 4 of NADH dehydrogenase (MTND4), associated with maternally inherited Leber's hereditary optic neuropathy (LHON). Henceforth, a novel conceptual "mitochondrial genetics", separate from mendelian genetics, arose, based on three features of mtDNA: (1) polyplasmy; (2) maternal inheritance; and (3) mitotic segregation. Diagnosis of mtDNA-related diseases became possible through genetic analysis and experimental approaches involving histochemical staining of muscle or brain sections, single-fiber polymerase chain reaction (PCR) of mtDNA, and the creation of patient-derived "cybrid" (cytoplasmic hybrid) immortal fibroblast cell lines. The availability of the above-mentioned techniques along with the novel sensitivity of clinicians to such disorders led to the characterization of a constantly growing number of pathologies. Here is traced a brief historical perspective on the discovery of autonomous pathogenic mtDNA mutations and on the related mendelian pathology altering mtDNA integrity.

Keywords: mendelian and maternal inheritance; mitochondrial pathologies; mtDNA mutations.

Publication types

  • Historical Article

MeSH terms

  • DNA, Mitochondrial / genetics*
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / history*
  • Mitochondrial Diseases / pathology*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Mutation*


  • DNA, Mitochondrial
  • Mitochondrial Proteins