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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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Autor principal: DiMauro, Salvatore
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
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.
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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
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