A Brief History of Mitochondrial Pathologies
Open Access
- 12 November 2019
- journal article
- perspective
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 20 (22), 5643
- https://doi.org/10.3390/ijms20225643
Abstract
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.This publication has 54 references indexed in Scilit:
- Biparental Inheritance of Mitochondrial DNA in HumansProceedings of the National Academy of Sciences of the United States of America, 2018
- The clinical maze of mitochondrial neurologyNature Reviews Neurology, 2013
- Optical Imaging Techniques (Histochemical, Immunohistochemical, and In Situ Hybridization Staining Methods) to Visualize MitochondriaMethods in Cell Biology, 2007
- Risk of developing a mitochondrial DNA deletion disorderThe Lancet, 2004
- Mitochondrial Respiratory-Chain DiseasesThe New England Journal of Medicine, 2003
- Exercise Intolerance Due to Mutations in the CytochromebGene of Mitochondrial DNAThe New England Journal of Medicine, 1999
- Mitochondrial DNA Mutation Associated with Leber's Hereditary Optic NeuropathyScience, 1988
- Deletions of mitochondrial DNA in Kearns‐Sayre syndromeNeurology, 1988
- Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathiesNature, 1988
- Maternal inheritance of human mitochondrial DNA.Proceedings of the National Academy of Sciences of the United States of America, 1980