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LHON: Mitochondrial Mutations and More
Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disorder leading to severe visual impairment or even blindness by death of retinal ganglion cells (RGCs). The primary cause of the disease is usually a mutation of the mitochondrial genome (mtDNA) causing a single amino acid exchange in o...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Bentham Science Publishers Ltd
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129042/ https://www.ncbi.nlm.nih.gov/pubmed/21886454 http://dx.doi.org/10.2174/138920211794520150 |
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author | Kirches, E |
author_facet | Kirches, E |
author_sort | Kirches, E |
collection | PubMed |
description | Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disorder leading to severe visual impairment or even blindness by death of retinal ganglion cells (RGCs). The primary cause of the disease is usually a mutation of the mitochondrial genome (mtDNA) causing a single amino acid exchange in one of the mtDNA-encoded subunits of NADH:ubiquinone oxidoreductase, the first complex of the electron transport chain. It was thus obvious to accuse neuronal energy depletion as the most probable mediator of neuronal death. The group of Valerio Carelli and other authors have nicely shown that energy depletion shapes the cell fate in a LHON cybrid cell model. However, the cybrids used were osteosarcoma cells, which do not fully model neuronal energy metabolism. Although complex I mutations may cause oxidative stress, a potential pathogenetic role of the latter was less taken into focus. The hypothesis of bioenergetic failure does not provide a simple explanation for the relatively late disease onset and for the incomplete penetrance, which differs remarkably between genders. It is assumed that other genetic and environmental factors are needed in addition to the ‘primary LHON mutations’ to elicit RGC death. Relevant nuclear modifier genes have not been identified so far. The review discusses the unresolved problems of a pathogenetic hypothesis based on ATP decline and/or ROS-induced apoptosis in RGCs. |
format | Online Article Text |
id | pubmed-3129042 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Bentham Science Publishers Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-31290422011-09-01 LHON: Mitochondrial Mutations and More Kirches, E Curr Genomics Article Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disorder leading to severe visual impairment or even blindness by death of retinal ganglion cells (RGCs). The primary cause of the disease is usually a mutation of the mitochondrial genome (mtDNA) causing a single amino acid exchange in one of the mtDNA-encoded subunits of NADH:ubiquinone oxidoreductase, the first complex of the electron transport chain. It was thus obvious to accuse neuronal energy depletion as the most probable mediator of neuronal death. The group of Valerio Carelli and other authors have nicely shown that energy depletion shapes the cell fate in a LHON cybrid cell model. However, the cybrids used were osteosarcoma cells, which do not fully model neuronal energy metabolism. Although complex I mutations may cause oxidative stress, a potential pathogenetic role of the latter was less taken into focus. The hypothesis of bioenergetic failure does not provide a simple explanation for the relatively late disease onset and for the incomplete penetrance, which differs remarkably between genders. It is assumed that other genetic and environmental factors are needed in addition to the ‘primary LHON mutations’ to elicit RGC death. Relevant nuclear modifier genes have not been identified so far. The review discusses the unresolved problems of a pathogenetic hypothesis based on ATP decline and/or ROS-induced apoptosis in RGCs. Bentham Science Publishers Ltd 2011-03 /pmc/articles/PMC3129042/ /pubmed/21886454 http://dx.doi.org/10.2174/138920211794520150 Text en ©2011 Bentham Science Publishers Ltd. http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Kirches, E LHON: Mitochondrial Mutations and More |
title | LHON: Mitochondrial Mutations and More |
title_full | LHON: Mitochondrial Mutations and More |
title_fullStr | LHON: Mitochondrial Mutations and More |
title_full_unstemmed | LHON: Mitochondrial Mutations and More |
title_short | LHON: Mitochondrial Mutations and More |
title_sort | lhon: mitochondrial mutations and more |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129042/ https://www.ncbi.nlm.nih.gov/pubmed/21886454 http://dx.doi.org/10.2174/138920211794520150 |
work_keys_str_mv | AT kirchese lhonmitochondrialmutationsandmore |