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A Brief History of Mitochondrial Pathologies
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 re...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888695/ https://www.ncbi.nlm.nih.gov/pubmed/31718067 http://dx.doi.org/10.3390/ijms20225643 |
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author | DiMauro, Salvatore |
author_facet | DiMauro, Salvatore |
author_sort | DiMauro, Salvatore |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6888695 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68886952019-12-09 A Brief History of Mitochondrial Pathologies DiMauro, Salvatore Int J Mol Sci Perspective 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. MDPI 2019-11-12 /pmc/articles/PMC6888695/ /pubmed/31718067 http://dx.doi.org/10.3390/ijms20225643 Text en © 2019 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Perspective DiMauro, Salvatore A Brief History of Mitochondrial Pathologies |
title | A Brief History of Mitochondrial Pathologies |
title_full | A Brief History of Mitochondrial Pathologies |
title_fullStr | A Brief History of Mitochondrial Pathologies |
title_full_unstemmed | A Brief History of Mitochondrial Pathologies |
title_short | A Brief History of Mitochondrial Pathologies |
title_sort | brief history of mitochondrial pathologies |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888695/ https://www.ncbi.nlm.nih.gov/pubmed/31718067 http://dx.doi.org/10.3390/ijms20225643 |
work_keys_str_mv | AT dimaurosalvatore abriefhistoryofmitochondrialpathologies AT dimaurosalvatore briefhistoryofmitochondrialpathologies |